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Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review

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Abstract

Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations.

Graphical Abstract

This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS.

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References

  • Adams RA, Bauer J, Flick MJ, Sikorski SL, Nuriel T, Lassmann H, Degen JL, Akassoglou K (2007) The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med 204(3):571–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agrawal S, Zhao Q (1998) Antisense therapeutics. Curr Opin Chem Biol 2(4):519–528

    Article  CAS  PubMed  Google Scholar 

  • Alahmad G, Aljohani S, Najjar MF (2020) Ethical challenges regarding the use of stem cells: interviews with researchers from Saudi Arabia. BMC Med Ethics 21(1):35

    Article  PubMed  PubMed Central  Google Scholar 

  • Alanazi A, Alassiri M, Jawdat D, Almalik Y (2022) Mesenchymal stem cell therapy: a review of clinical trials for multiple sclerosis. Regen Ther 21:201–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alexeev V, Donahue A, Uitto J, Igoucheva O (2013) Analysis of chemotactic molecules in bone marrow-derived mesenchymal stem cells and the skin: Ccl27-Ccr10 axis as a basis for targeting to cutaneous tissues. Cytotherapy 15(2):171–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almeida-Porada G, Atala AJ, Porada CD (2020) Therapeutic mesenchymal stromal cells for immunotherapy and for gene and drug delivery. Mol Ther Methods Clin Dev 16:204–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • AlSawaftah NM, Awad NS, Pitt WG, Husseini GA (2022) pH-responsive nanocarriers in cancer therapy. Polymers (basel) 14:5

    Article  Google Scholar 

  • Alzate-Correa D, Lawrence WR, Salazar-Puerta A, Higuita-Castro N, Gallego-Perez D (2022) Nanotechnology-driven cell-based therapies in regenerative medicine. AAPS J 24(2):43

    Article  CAS  PubMed  Google Scholar 

  • Anjum S, Ishaque S, Fatima H, Farooq W, Hano C, Abbasi BH, Anjum I (2021) Emerging applications of nanotechnology in healthcare systems: grand challenges and perspectives. Pharmaceuticals (basel) 14:8

    Article  Google Scholar 

  • Ankam S, Lim CK, Yim EK (2015) Actomyosin contractility plays a role in MAP2 expression during nanotopography-directed neuronal differentiation of human embryonic stem cells. Biomaterials 47:20–28

    Article  CAS  PubMed  Google Scholar 

  • Ankam S, Suryana M, Chan LY, Moe AA, Teo BK, Law JB, Sheetz MP, Low HY, Yim EK (2013) Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage. Acta Biomater 9(1):4535–4545

    Article  CAS  PubMed  Google Scholar 

  • Arora P, Sindhu A, Dilbaghi N, Chaudhury A, Rajakumar G, Rahuman AA (2012) Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans. J Cell Mol Med 16(9):1991–2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, Bence-Bruckler I, Birch P, Bredeson C, Chen J, Fergusson D, Halpenny M, Hamelin L, Huebsch L, Hutton B, Laneuville P, Lapierre Y, Lee H, Martin L, McDiarmid S, O’Connor P, Ramsay T, Sabloff M, Walker L, Freedman MS (2016) Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet 388(10044):576–585

    Article  PubMed  Google Scholar 

  • Auffinger B, Morshed R, Tobias A, Cheng Y, Ahmed AU, Lesniak MS (2013) Drug-loaded nanoparticle systems and adult stem cells: a potential marriage for the treatment of malignant glioma? Oncotarget 4(3):378–396

    Article  PubMed  PubMed Central  Google Scholar 

  • Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153(3):198–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banerjee S, Xie N, Cui H, Tan Z, Yang S, Icyuz M, Abraham E, Liu G (2013) MicroRNA let-7c regulates macrophage polarization. J Immunol 190(12):6542–6549

    Article  CAS  PubMed  Google Scholar 

  • Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, Calabresi PA, Waubant E, Hauser SL, Zhang J, Smith CH (2010) Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 67(4):452–461

    Article  CAS  PubMed  Google Scholar 

  • Baranzini SE, Elfstrom C, Chang SY, Butunoi C, Murray R, Higuchi R, Oksenberg JR (2000) Transcriptional analysis of multiple sclerosis brain lesions reveals a complex pattern of cytokine expression. J Immunol 165(11):6576–6582

    Article  CAS  PubMed  Google Scholar 

  • Barreca MM, Spinello W, Cavalieri V, Turturici G, Sconzo G, Kaur P, Tinnirello R, Asea AA, Geraci F (2017) Extracellular Hsp70 enhances mesoangioblast migration via an autocrine signaling pathway. J Cell Physiol 232(7):1845–1861

    Article  CAS  PubMed  Google Scholar 

  • Barros D, Conde-Sousa E, Goncalves AM, Han WM, Garcia AJ, Amaral IF, Pego AP (2019) Engineering hydrogels with affinity-bound laminin as 3D neural stem cell culture systems. Biomater Sci 7(12):5338–5349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barth KA, Wilson SW (1995) Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain. Development 121(6):1755–1768

    Article  CAS  PubMed  Google Scholar 

  • Bawa R (2011) Regulating nanomedicine - can the FDA handle it? Curr Drug Deliv 8(3):227–234

    Article  CAS  PubMed  Google Scholar 

  • Bayda S, Adeel M, Tuccinardi T, Cordani M, Rizzolio F (2019) The history of nanoscience and nanotechnology: from chemical-physical applications to nanomedicine. Molecules 25:1

    Article  Google Scholar 

  • Beddoes CM, Case CP, Briscoe WH (2015) Understanding nanoparticle cellular entry: a physicochemical perspective. Adv Colloid Interface Sci 218:48–68

    Article  CAS  PubMed  Google Scholar 

  • Beebe DJ, Mensing GA, Walker GM (2002) Physics and applications of microfluidics in biology. Annu Rev Biomed Eng 4:261–286

    Article  CAS  PubMed  Google Scholar 

  • Ben-Hur T, Idelson M, Khaner H, Pera M, Reinhartz E, Itzik A, Reubinoff BE (2004) Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian rats. Stem Cells 22(7):1246–1255

    Article  PubMed  Google Scholar 

  • Benzin H, Schumann S, Richter A, Kier J, Kruse C, Matthiessen AE (2021) Evaluation of human skin-derived stem cell characteristics after non-invasive quantum dot labeling. Cell Physiol Biochem 55(4):387–399

    Article  CAS  PubMed  Google Scholar 

  • Bernal A, Arranz L (2018) Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cell Mol Life Sci 75(12):2177–2195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boffa G, Signori A, Massacesi L, Mariottini A, Sbragia E, Cottone S, Amato MP, Gasperini C, Moiola L, Meletti S, Repice AM, Brescia Morra V, Salemi G, Patti F, Filippi M, De Luca G, Lus G, Zaffaroni M, Sola P, Conte A, Nistri R, Aguglia U, Granella F, Galgani S, Caniatti LM, Lugaresi A, Romano S, Iaffaldano P, Cocco E, Saccardi R, Angelucci E, Trojano M, Mancardi GL, Sormani MP, Inglese M, Italian BMTMSSG, M. S. R. the Italian, (2023) Hematopoietic stem cell transplantation in people with active secondary progressive multiple sclerosis. Neurology 100(11):e1109–e1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown C, McKee C, Halassy S, Kojan S, Feinstein DL, Chaudhry GR (2021) Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Stem Cell Res Ther 12(1):499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, Fagius J, Rose J, Nelson F, Barreira AA, Carlson K, Han X, Moraes D, Morgan A, Quigley K, Yaung K, Buckley R, Alldredge C, Clendenan A, Calvario MA, Henry J, Jovanovic B, Helenowski IB (2019) Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial. JAMA 321(2):165–174

    Article  PubMed  PubMed Central  Google Scholar 

  • Burt RK, Balabanov R, Han X, Sharrack B, Morgan A, Quigley K, Yaung K, Helenowski IB, Jovanovic B, Spahovic D, Arnautovic I, Lee DC, Benefield BC, Futterer S, Oliveira MC, Burman J (2015) Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA 313(3):275–284

    Article  PubMed  Google Scholar 

  • Cai J, St Amand T, Yin H, Guo H, Li G, Zhang Y, Chen Y, Qiu M (1999) Expression and regulation of the chicken Nkx-6.2 homeobox gene suggest its possible involvement in the ventral neural patterning and cell fate specification. Dev Dyn 216(4–5):459–468

    Article  CAS  PubMed  Google Scholar 

  • Cai J, Zhu Q, Zheng K, Li H, Qi Y, Cao Q, Qiu M (2010) Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes. Glia 58(4):458–468

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao L, Xu H, Wang G, Liu M, Tian D, Yuan Z (2019) Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization. Int Immunopharmacol 72:264–274

    Article  CAS  PubMed  Google Scholar 

  • Cao Y, Xu Y, Chen C, Xie H, Lu H, Hu J (2021) Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis. Stem Cell Res Ther 12(1):20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carballo GB, Honorato JR, de Lopes GPF, Spohr T (2018) A highlight on sonic hedgehog pathway. Cell Commun Signal 16(1):11

    Article  PubMed  PubMed Central  Google Scholar 

  • Caudle WMJN, o. M. (2017) Occupational metal exposure and parkinsonism. Adv Neurobiol 2017(18):143–158

    Article  Google Scholar 

  • Cedola A, Bravin A, Bukreeva I, Fratini M, Pacureanu A, Mittone A, Massimi L, Cloetens P, Coan P, Campi G, Spano R, Brun F, Grigoryev V, Petrosino V, Venturi C, Mastrogiacomo M, Kerlero de Rosbo N, Uccelli A (2017) X-ray phase contrast tomography reveals early vascular alterations and neuronal loss in a multiple sclerosis model. Sci Rep 7(1):5890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chanoumidou K, Hernandez-Rodriguez B, Windener F, Thomas C, Stehling M, Mozafari S, Albrecht S, Ottoboni L, Antel J, Kim KP, Velychko S, Cui QL, Xu YKT, Martino G, Winkler J, Scholer HR, Baron-Van Evercooren A, Boespflug-Tanguy O, Vaquerizas JM, Ehrlich M, Kuhlmann T (2021) One-step reprogramming of human fibroblasts into oligodendrocyte-like cells by SOX10, OLIG2, and NKX6.2. Stem Cell Reports 16(4):771–783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen G, Courey AJ (2000) Groucho/TLE family proteins and transcriptional repression. Gene 249(1–2):1–16

    Article  CAS  PubMed  Google Scholar 

  • Chen SY, Cheng AMS, Zhang Y, Zhu YT, He H, Mahabole M, Tseng SCG (2019) Pax 6 controls neural crest potential of limbal niche cells to support self-renewal of limbal epithelial stem cells. Sci Rep 9(1):9763

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen W, Han S, Qian W, Weng S, Yang H, Sun Y, Villa-Diaz LG, Krebsbach PH, Fu J (2018) Nanotopography regulates motor neuron differentiation of human pluripotent stem cells. Nanoscale 10(7):3556–3565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Huang Y, Han J, Yu L, Li Y, Lu Z, Li H, Liu Z, Shi C, Duan F, Xiao Y (2016) Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res 64(4):831–840

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Shao Y, Li X, Zhao G, Fu J (2014) Nanotopographical surfaces for stem cell fate control: engineering mechanobiology from the bottom. Nano Today 9(6):759–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Villa-Diaz LG, Sun Y, Weng S, Kim JK, Lam RH, Han L, Fan R, Krebsbach PH, Fu J (2012) Nanotopography influences adhesion, spreading, and self-renewal of human embryonic stem cells. ACS Nano 6(5):4094–4103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6(4):662–668

    Article  CAS  PubMed  Google Scholar 

  • Choi SY, Song MS, Ryu PD, Lam AT, Joo SW, Lee SY (2015) Gold nanoparticles promote osteogenic differentiation in human adipose-derived mesenchymal stem cells through the Wnt/beta-catenin signaling pathway. Int J Nanomed 10:4383–4392

    CAS  Google Scholar 

  • Choudhry Z, Rikani AA, Choudhry AM, Tariq S, Zakaria F, Asghar MW, Sarfraz MK, Haider K, Shafiq AA, Mobassarah NJ (2014) Sonic hedgehog signalling pathway: a complex network. Ann Neurosci 21(1):28–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu F, Shi M, Zheng C, Shen D, Zhu J, Zheng X, Cui L (2018) The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol 318:1–7

    Article  CAS  PubMed  Google Scholar 

  • Cohen CB, Cohen PJ (2010) International stem cell tourism and the need for effective regulation. Part I: Stem cell tourism in Russia and India: clinical research, innovative treatment, or unproven hype? Kennedy Inst Ethics J 20(1):27–49

    Article  PubMed  Google Scholar 

  • Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S (2012) Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol 11(2):150–156

    Article  PubMed  PubMed Central  Google Scholar 

  • Corti S, Nizzardo M, Nardini M, Donadoni C, Locatelli F, Papadimitriou D, Salani S, Del Bo R, Ghezzi S, Strazzer S, Bresolin N, Comi GP (2007) Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Exp Neurol 205(2):547–562

    Article  CAS  PubMed  Google Scholar 

  • Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noel D (2017) Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep 7(1):16214

    Article  PubMed  PubMed Central  Google Scholar 

  • Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313

    Article  CAS  PubMed  Google Scholar 

  • D’Angelo F, Armentano I, Mattioli S, Crispoltoni L, Tiribuzi R, Cerulli GG, Palmerini CA, Kenny JM, Martino S, Orlacchio A (2010) Micropatterned hydrogenated amorphous carbon guides mesenchymal stem cells towards neuronal differentiation. Eur Cell Mater 20:231–244

    Article  CAS  PubMed  Google Scholar 

  • Dalby MJ, Gadegaard N, Oreffo RO (2014) Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. Nat Mater 13(6):558–569

    Article  CAS  PubMed  Google Scholar 

  • Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, Wilkinson CD, Oreffo RO (2007) The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 6(12):997–1003

    Article  CAS  PubMed  Google Scholar 

  • Daley WP, Peters SB, Larsen M (2008) Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci 121(Pt 3):255–264

    Article  CAS  PubMed  Google Scholar 

  • Dardir K, Rathnam C, Lee KB (2017) NanoScript: A Versatile Nanoparticle-Based Synthetic Transcription Factor for Innovative Gene Manipulation. Methods Mol Biol 1570:239–249

    Article  CAS  PubMed  Google Scholar 

  • Delyagina E, Li W, Ma N, Steinhoff G (2011) Magnetic targeting strategies in gene delivery. Nanomedicine (lond) 6(9):1593–1604

    Article  CAS  PubMed  Google Scholar 

  • Deng M, James R, Laurencin CT, Kumbar SG (2012) Nanostructured polymeric scaffolds for orthopaedic regenerative engineering. IEEE Trans Nanobiosci 11(1):3–14

    Article  Google Scholar 

  • Dhib-Jalbut S (2002) Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 58(8 Suppl 4):S3-9

    CAS  PubMed  Google Scholar 

  • Dias de Sousa MA, Desiderio CS, da Silva Catarino J, Trevisan RO, Alves da Silva DA, Rocha VFR, Bovi WG, Timoteo RP, Bonatti RCF, da Silva AE, Fernandez AL, Sales-Campos H, Rodrigues Junior V, da Silva MV, de Oliveira CJF (2022) Role of cytokines, chemokines and IFN-gamma(+) IL-17(+) double-positive CD4(+) T cells in patients with multiple sclerosis. Biomedicines 10:9

    Article  Google Scholar 

  • Dong Y, Wu X, Chen X, Zhou P, Xu F, Liang W (2021) Nanotechnology shaping stem cell therapy: recent advances, application, challenges, and future outlook. Biomed Pharmacother 137:111236

    Article  CAS  PubMed  Google Scholar 

  • Douvaras P, Wang J, Zimmer M, Hanchuk S, O’Bara MA, Sadiq S, Sim FJ, Goldman J, Fossati VJS (2014) Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Rep 3(2):250–259

    Article  CAS  Google Scholar 

  • Duarte Azevedo M, Sander S, Tenenbaum L (2020) GDNF, a neuron-derived factor upregulated in glial cells during disease. J Clin Med 9:2

    Article  Google Scholar 

  • Ellis P, Fagan BM, Magness ST, Hutton S, Taranova O, Hayashi S, McMahon A, Rao M, Pevny L (2004) SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. Dev Neurosci 26(2–4):148–165

    Article  CAS  PubMed  Google Scholar 

  • Emery B, Lu QR (2015) Transcriptional and epigenetic regulation of oligodendrocyte development and myelination in the central nervous system. Cold Spring Harb Perspect Biol 7(9):a020461

    Article  PubMed  PubMed Central  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    Article  CAS  PubMed  Google Scholar 

  • Ericson J, Muhr J, Placzek M, Lints T, Jessell TM, Edlund T (1995) Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Cell 81(5):747–756

    Article  CAS  PubMed  Google Scholar 

  • Esfahani SN, Resto Irizarry AM, Xue X, Lee SB, Shao Y, Fu J (2021) Micro/nanoengineered technologies for human pluripotent stem cells maintenance and differentiation. Nano Today 41:1

    Article  Google Scholar 

  • Fan Y, Herr F, Vernochet A, Mennesson B, Oberlin E, Durrbach A (2019) Human fetal liver mesenchymal stem cell-derived exosomes impair natural killer cell function. Stem Cells Dev 28(1):44–55

    Article  CAS  PubMed  Google Scholar 

  • Farjadian F, Ghasemi A, Gohari O, Roointan A, Karimi M, Hamblin MR (2019) Nanopharmaceuticals and nanomedicines currently on the market: challenges and opportunities. Nanomedicine (lond) 14(1):93–126

    Article  CAS  PubMed  Google Scholar 

  • Favretto ME, Wallbrecher R, Schmidt S, van de Putte R, Brock R (2014) Glycosaminoglycans in the cellular uptake of drug delivery vectors - bystanders or active players? J Control Release 180:81–90

    Article  CAS  PubMed  Google Scholar 

  • Ferent J, Zimmer C, Durbec P, Ruat M, Traiffort E (2013) Sonic Hedgehog signaling is a positive oligodendrocyte regulator during demyelination. J Neurosci 33(5):1759–1772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferri AL, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi PP, Sala M, DeBiasi S, Nicolis SK (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131(15):3805–3819

    Article  CAS  PubMed  Google Scholar 

  • Filipi M, Jack S (2020) Interferons in the treatment of multiple sclerosis: a clinical efficacy, safety, and tolerability update. Int J MS Care 22(4):165–172

    Article  PubMed  Google Scholar 

  • Flora S (2017) The applications, neurotoxicity, and related mechanism of gold nanoparticles. Neurotoxicity of nanomaterials and nanomedicine. Elsevier, Amsterdam, pp 179–203

    Chapter  Google Scholar 

  • Foglio B, Rossini L, Garbelli R, Regondi MC, Mercurio S, Bertacchi M, Avagliano L, Bulfamante G, Coras R, Maiorana A, Nicolis S, Studer M, Frassoni C (2021) Dynamic expression of NR2F1 and SOX2 in developing and adult human cortex: comparison with cortical malformations. Brain Struct Funct 226(4):1303–1322

    Article  CAS  PubMed  Google Scholar 

  • Franklin RJ (2012) Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol 8(11):624–634

    Article  PubMed  Google Scholar 

  • Gaillard PJ, Appeldoorn CC, Rip J, Dorland R, van der Pol SM, Kooij G, de Vries HE, Reijerkerk A (2012) Enhanced brain delivery of liposomal methylprednisolone improved therapeutic efficacy in a model of neuroinflammation. J Control Release 164(3):364–369

    Article  CAS  PubMed  Google Scholar 

  • Gao Z, Zhang C, Feng Z, Liu Z, Yang Y, Yang K, Chen L, Yao R (2022) C1q inhibits differentiation of oligodendrocyte progenitor cells via Wnt/beta-catenin signaling activation in a cuprizone-induced mouse model of multiple sclerosis. Exp Neurol 348:113947

    Article  CAS  PubMed  Google Scholar 

  • Garcia E, Sanchez-Noriega S, Gonzalez-Pacheco G, Gonzalez-Vazquez AN, Ibarra A, Rodriguez-Barrera R (2023) Recent advances in the combination of cellular therapy with stem cells and nanoparticles after a spinal cord injury. Front Neurol 14:1127878

    Article  PubMed  PubMed Central  Google Scholar 

  • Genchi A, Brambilla E, Sangalli F, Radaelli M, Bacigaluppi M, Furlan R, Andolfo A, Drago D, Magagnotti C, Scotti GM, Greco R, Vezzulli P, Ottoboni L, Bonopane M, Capilupo D, Ruffini F, Belotti D, Cabiati B, Cesana S, Matera G, Leocani L, Martinelli V, Moiola L, Vago L, Panina-Bordignon P, Falini A, Ciceri F, Uglietti A, Sormani MP, Comi G, Battaglia MA, Rocca MA, Storelli L, Pagani E, Gaipa G, Martino G (2023) Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med 29(1):75–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghosh G, Panicker L (2021) Protein-nanoparticle interactions and a new insight. Soft Matter 17(14):3855–3875

    Article  CAS  PubMed  Google Scholar 

  • Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA (2010) Gold nanoparticles for biology and medicine. Angew Chem Int Ed Engl 49(19):3280–3294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giovannoni G (2018) Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol 31(3):233–243

    Article  CAS  PubMed  Google Scholar 

  • Goverman J (2009) Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9(6):393–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grigoriadis N, van Pesch V, Paradig MSG (2015) A basic overview of multiple sclerosis immunopathology. Eur J Neurol 22(Suppl 2):3–13

    Article  PubMed  Google Scholar 

  • Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5(1):17–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gustafson HH, Holt-Casper D, Grainger DW, Ghandehari H (2015) Nanoparticle uptake: the phagocyte problem. Nano Today 10(4):487–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hao P, Duan H, Hao F, Chen L, Sun M, Fan KS, Sun YE, Williams D, Yang Z, Li X (2017) Neural repair by NT3-chitosan via enhancement of endogenous neurogenesis after adult focal aspiration brain injury. Biomaterials 140:88–102

    Article  CAS  PubMed  Google Scholar 

  • Harris VK, Stark J, Vyshkina T, Blackshear L, Joo G, Stefanova V, Sara G, Sadiq SA (2018) Phase I trial of intrathecal mesenchymal stem cell-derived neural progenitors in progressive multiple sclerosis. EBioMedicine 29:23–30

    Article  PubMed  PubMed Central  Google Scholar 

  • Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L, Opera I, Investigators OIC (2017) Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 376(3):221–234

    Article  CAS  PubMed  Google Scholar 

  • Hocking AM (2015) The role of chemokines in mesenchymal stem cell homing to wounds. Adv Wound Care (new Rochelle) 4(11):623–630

    Article  PubMed  Google Scholar 

  • Hong YJ, Do JT (2019) Neural lineage differentiation from pluripotent stem cells to mimic human brain tissues. Front Bioeng Biotechnol 7:400

    Article  PubMed  PubMed Central  Google Scholar 

  • Hosseini Shamili F, Alibolandi M, Rafatpanah H, Abnous K, Mahmoudi M, Kalantari M, Taghdisi SM, Ramezani M (2019) Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score. J Control Release 299:149–164

    Article  CAS  PubMed  Google Scholar 

  • Huang CC, Kang M, Shirazi S, Lu Y, Cooper LF, Gajendrareddy P, Ravindran S (2021) 3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels. Acta Biomater 126:199–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Zhang L (2019) Neural stem cell therapies and hypoxic-ischemic brain injury. Prog Neurobiol 173:1–17

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Zhang F, Wang Y, Sun X, Choi KY, Liu D, Choi JS, Shin TH, Cheon J, Niu G, Chen X (2014) Design considerations of iron-based nanoclusters for noninvasive tracking of mesenchymal stem cell homing. ACS Nano 8(5):4403–4414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalali A, Bassuk AG, Kan L, Israsena N, Mukhopadhyay A, McGuire T, Kessler JA (2011) HeyL promotes neuronal differentiation of neural progenitor cells. J Neurosci Res 89(3):299–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalilian B, Einarsson HB, Vorup-Jensen T (2012) Glatiramer acetate in treatment of multiple sclerosis: a toolbox of random co-polymers for targeting inflammatory mechanisms of both the innate and adaptive immune system? Int J Mol Sci 13(11):14579–14605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarrar W, Dias JM, Ericson J, Arnold HH, Holz A (2015) Nkx2.2 and Nkx2.9 are the key regulators to determine cell fate of branchial and visceral motor neurons in caudal hindbrain. PLoS ONE 10(4):e0124408

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang HR, Milovanovic M, Allan D, Niedbala W, Besnard AG, Fukada SY, Alves-Filho JC, Togbe D, Goodyear CS, Linington C, Xu D, Lukic ML, Liew FY (2012) IL-33 attenuates EAE by suppressing IL-17 and IFN-gamma production and inducing alternatively activated macrophages. Eur J Immunol 42(7):1804–1814

    Article  CAS  PubMed  Google Scholar 

  • Jiang M, Yu D, Xie B, Huang H, Lu W, Qiu M, Dai ZM (2020) WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression. Mol Brain 13(1):155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaskow, B. J. and C. Baecher-Allan (2018). "Effector T Cells in Multiple Sclerosis." Cold Spring Harb Perspect Med 8:4.

  • Katoh Y, Katoh M (2006) WNT antagonist, SFRP1, is Hedgehog signaling target. Int J Mol Med 17(1):171–175

    CAS  PubMed  Google Scholar 

  • Keung AJ, Asuri P, Kumar S, Schaffer DV (2012) Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells. Integr Biol (camb) 4(9):1049–1058

    Article  CAS  PubMed  Google Scholar 

  • Khan AA, Huat TJ, Al Mutery A, El-Serafi AT, Kacem HH, Abdallah SH, Reza MF, Abdullah JM, Jaafar H (2020) Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF. Cell Biosci 10:126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klibanov AL, Maruyama K, Torchilin VP, Huang L (1990) Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 268(1):235–237

    Article  CAS  PubMed  Google Scholar 

  • Kondelkova K, Vokurkova D, Krejsek J, Borska L, Fiala Z, Ctirad A (2010) Regulatory T cells (TREG) and their roles in immune system with respect to immunopathological disorders. Acta Med (hradec Kralove) 53(2):73–77

    Article  CAS  Google Scholar 

  • Kotter MR, Li WW, Zhao C, Franklin RJ (2006) Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci 26(1):328–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotter MR, Stadelmann C, Hartung HP (2011) Enhancing remyelination in disease–can we wrap it up? Brain 134(Pt 7):1882–1900

    Article  PubMed  Google Scholar 

  • Kshitiz DH, Kim DJ, Beebe and A. Levchenko, (2011) Micro- and nanoengineering for stem cell biology: the promise with a caution. Trends Biotechnol 29(8):399–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuhn S, Gritti L, Crooks D, Dombrowski Y (2019) Oligodendrocytes in development, myelin generation and beyond. Cells 8:11

    Article  Google Scholar 

  • Kulkarni S, Micci MA, Leser J, Shin C, Tang SC, Fu YY, Liu L, Li Q, Saha M, Li C, Enikolopov G, Becker L, Rakhilin N, Anderson M, Shen X, Dong X, Butte MJ, Song H, Southard-Smith EM, Kapur RP, Bogunovic M, Pasricha PJ (2017) Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc Natl Acad Sci U S A 114(18):E3709–E3718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumari S, Vermeulen S, van der Veer B, Carlier A, de Boer J, Subramanyam D (2018) Shaping cell fate: influence of topographical substratum properties on embryonic stem cells. Tissue Eng Part B Rev 24(4):255–266

    Article  PubMed  Google Scholar 

  • Kwak G, Cheng J, Kim H, Song S, Lee SJ, Yang Y, Jeong JH, Lee JE, Messersmith PB, Kim SH (2022) Sustained exosome-guided macrophage polarization using hydrolytically degradable PEG hydrogels for cutaneous wound healing: identification of key proteins and mirnas, and sustained release formulation. Small 18(15):e2200060

    Article  PubMed  Google Scholar 

  • La Mantia L, Di Pietrantonj C, Rovaris M, Rigon G, Frau S, Berardo F, Gandini A, Longobardi A, Weinstock-Guttman B, Vaona A (2016) Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev 11(11):CD009333

    PubMed  Google Scholar 

  • La Mantia L, Munari LM, Lovati R (2010) Glatiramer acetate for multiple sclerosis. Cochrane Database Syst Rev 5:CD004678

    Google Scholar 

  • Labusca L, Herea DD, Mashayekhi K (2018) Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives. World J Stem Cells 10(5):43–56

    Article  PubMed  PubMed Central  Google Scholar 

  • Lalitha S, Basu B, Surya S, Meera V, Riya PA, Parvathy S, Das AV, Sivakumar KC, Nelson-Sathi S, James J (2020) Pax6 modulates intra-retinal axon guidance and fasciculation of retinal ganglion cells during retinogenesis. Sci Rep 10(1):16075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lammermann T, Sixt M (2009) Mechanical modes of “amoeboid” cell migration. Curr Opin Cell Biol 21(5):636–644

    Article  PubMed  Google Scholar 

  • Lee MR, Kwon KW, Jung H, Kim HN, Suh KY, Kim K, Kim KS (2010) Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays. Biomaterials 31(15):4360–4366

    Article  CAS  PubMed  Google Scholar 

  • Levy R, Shaheen U, Cesbron Y, See V (2010) Gold nanoparticles delivery in mammalian live cells: a critical review. Nano Rev 1:1

    Article  Google Scholar 

  • Li J, Martin F (2017) Current perspective on nanomaterial-induced adverse effects: neurotoxicity as a case example. Neurotoxicity of nanomaterials and nanomedicine. Elsevier, Amsterdam, pp 75–98

    Chapter  Google Scholar 

  • Li M, Zhang P, Zhang D (2018) PVDF piezoelectric neural conduit incorporated pre-differentiated adipose-derived stem cells may accelerate the repair of peripheral nerve injury. Med Hypotheses 114:55–57

    Article  PubMed  Google Scholar 

  • Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Munch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541(7638):481–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin PL, Flynn JL (2015) CD8 T cells and Mycobacterium tuberculosis infection. Semin Immunopathol 37(3):239–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Xue W, Ge G, Luo X, Li Y, Xiang H, Ding X, Tian P, Tian X (2010) Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1alpha in MSCs. Biochem Biophys Res Commun 401(4):509–515

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Ren Z, Meng X, Xu YJJ (2022) Substrate topography regulates extracellular matrix component secretion by bone marrow-derived mesenchymal stem cells. J Sci 7(2):100437

    CAS  Google Scholar 

  • Liu Y, Rao M (2003) Oligodendrocytes, GRPs and MNOPs. Trends Neurosci 26(8):410–412

    Article  PubMed  Google Scholar 

  • Liu Y, Yang G, Jin S, Xu L, Zhao CX (2020) Development of high-drug-loading nanoparticles. ChemPlusChem 85(9):2143–2157

    Article  CAS  PubMed  Google Scholar 

  • Llufriu S, Sepúlveda M, Blanco Y, Marín P, Moreno B, Berenguer J, Gabilondo I, Martínez-Heras E, Sola-Valls N, J.-A. J. P. o. Arnaiz, (2014) Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis. PLoS ONE 9(12):e113936

    Article  PubMed  PubMed Central  Google Scholar 

  • Lorentzen AR, Karlsen TH, Olsson M, Smestad C, Mero IL, Woldseth B, Sun JY, Senitzer D, Celius EG, Thorsby E, Spurkland A, Lie BA, Harbo HF (2009) Killer immunoglobulin-like receptor ligand HLA-Bw4 protects against multiple sclerosis. Ann Neurol 65(6):658–666

    Article  CAS  PubMed  Google Scholar 

  • Louvi A, Artavanis-Tsakonas S (2006) Notch signalling in vertebrate neural development. Nat Rev Neurosci 7(2):93–102

    Article  CAS  PubMed  Google Scholar 

  • Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, Lubetzki C, Hartung HP, Montalban X, Uitdehaag BMJ, Merschhemke M, Li B, Putzki N, Liu FC, Haring DA, Kappos L, I. s. investigators, (2016) Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet 387(10023):1075–1084

    Article  CAS  PubMed  Google Scholar 

  • Ma L, Ke W, Liao Z, Feng X, Lei J, Wang K, Wang B, Li G, Luo R, Shi Y, Zhang W, Song Y, Sheng W, Yang C (2022) Small extracellular vesicles with nanomorphology memory promote osteogenesis. Bioact Mater 17:425–438

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ma X, Huang M, Zheng M, Dai C, Song Q, Zhang Q, Li Q, Gu X, Chen H, Jiang G, Yu Y, Liu X, Li S, Wang G, Chen H, Lu L, Gao X (2020) ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer’s disease. J Control Release 327:688–702

    Article  CAS  PubMed  Google Scholar 

  • Majumder J, Taratula O, Minko T (2019) Nanocarrier-based systems for targeted and site specific therapeutic delivery. Adv Drug Deliv Rev 144:57–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, Donelli A, Lugaresi A, Di Bartolomeo P, Rottoli MR, Rambaldi A, Amato MP, Massacesi L, Di Gioia M, Vuolo L, Curro D, Roccatagliata L, Filippi M, Aguglia U, Iacopino P, Farge D, Saccardi R et al (2015) Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology 84(10):981–988

    Article  CAS  PubMed  Google Scholar 

  • Mansour A, Romani M, Acharya AB, Rahman B, Verron E, Badran Z (2023) Drug delivery systems in regenerative medicine: an updated review. Pharmaceutics 15:2

    Article  Google Scholar 

  • Manuel M, Tan KB, Kozic Z, Molinek M, Marcos TS, Razak MFA, Dobolyi D, Dobie R, Henderson BEP, Henderson NC, Chan WK, Daw MI, Mason JO, Price DJ (2022) Pax6 limits the competence of developing cerebral cortical cells to respond to inductive intercellular signals. PLoS Biol 20(9):e3001563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marino A, Battaglini M, Tapeinos C, Larranaga A, Ciofani GJM (2022) Innovative nanotechnology tools for the functional control and tracking of human stem cells. Mater Today Adv 16:100298

    Article  CAS  Google Scholar 

  • Marsh SE, Blurton-Jones M (2017) Neural stem cell therapy for neurodegenerative disorders: the role of neurotrophic support. Neurochem Int 106:94–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martino G, Franklin RJ, Baron Van Evercooren A, Kerr DA et al (2010) Stem cell transplantation in multiple sclerosis: current status and future prospects. Nat Rev Neurol 6(5):247–255

    Article  PubMed  Google Scholar 

  • McIntyre LL, Greilach SA, Othy S, Sears-Kraxberger I, Wi B, Ayala-Angulo J, Vu E, Pham Q, Silva J, Dang K, Rezk F, Steward O, Cahalan MD, Lane TE, Walsh CM (2020) Regulatory T cells promote remyelination in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis following human neural stem cell transplant. Neurobiol Dis 140:104868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mercurio S, Serra L, Nicolis SK (2019) More than just stem cells: functional roles of the transcription factor Sox2 in differentiated glia and neurons. Int J Mol Sci 20:18

    Article  Google Scholar 

  • Ming X, Dupree JL, Gallo V, Chew LJ (2020) Sox17 promotes oligodendrocyte regeneration by dual modulation of Hedgehog and Wnt signaling. iScience 23(10):101592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mintzer MA, Simanek EE (2009) Nonviral vectors for gene delivery. Chem Rev 109(2):259–302

    Article  CAS  PubMed  Google Scholar 

  • Mokarizadeh A, Delirezh N, Morshedi A, Mosayebi G, Farshid AA, Mardani K (2012) Microvesicles derived from mesenchymal stem cells: potent organelles for induction of tolerogenic signaling. Immunol Lett 147(1–2):47–54

    Article  CAS  PubMed  Google Scholar 

  • Moll NM, Hong E, Fauveau M, Naruse M, Kerninon C, Tepavcevic V, Klopstein A, Seilhean D, Chew LJ, Gallo V, Nait Oumesmar B (2013) SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis. Glia 61(10):1659–1672

    Article  CAS  PubMed  Google Scholar 

  • Mondal D, Pradhan L, LaRussa VF (2004) Signal transduction pathways involved in the lineage-differentiation of NSCs: can the knowledge gained from blood be used in the brain? Cancer Invest 22(6):925–943

    Article  PubMed  Google Scholar 

  • Montelius A, Marmigere F, Baudet C, Aquino JB, Enerback S, Ernfors P (2007) Emergence of the sensory nervous system as defined by Foxs1 expression. Differentiation 75(5):404–417

    Article  CAS  PubMed  Google Scholar 

  • Mosleh-Shirazi S, Abbasi M, Moaddeli MR, Vaez A, Shafiee M, Kasaee SR, Amani AM, Hatam S (2022) Nanotechnology advances in the detection and treatment of cancer: an overview. Nanotheranostics 6(4):400–423

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakatani H, Martin E, Hassani H, Clavairoly A, Maire CL, Viadieu A, Kerninon C, Delmasure A, Frah M, Weber M, Nakafuku M, Zalc B, Thomas JL, Guillemot F, Nait-Oumesmar B, Parras C (2013) Ascl1/Mash1 promotes brain oligodendrogenesis during myelination and remyelination. J Neurosci 33(23):9752–9768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nazm Bojnordi M, Ghasemi HH, Akbari E (2015) Remyelination after Lysophosphatidyl choline-induced demyelination is stimulated by bone marrow stromal cell-derived oligoprogenitor cell transplantation. Cells Tissues Organs 200(5):300–306

    Article  CAS  PubMed  Google Scholar 

  • Ni X, Jia S, Duan X, Ding D, Li K (2018) Fluorescent nanoparticles for noninvasive stem cell tracking in regenerative medicine. J Biomed Nanotechnol 14(2):240–256

    Article  CAS  PubMed  Google Scholar 

  • Nicolay DJ, Doucette JR, Nazarali AJ (2004) Hoxb4 in oligodendrogenesis. Cell Mol Neurobiol 24(3):357–366

    Article  CAS  PubMed  Google Scholar 

  • Nisbet DR, Forsythe JS, Shen W, Finkelstein DI, Horne MK (2009) Review paper: a review of the cellular response on electrospun nanofibers for tissue engineering. J Biomater Appl 24(1):7–29

    Article  CAS  PubMed  Google Scholar 

  • Nyanguile O, Uesugi M, Austin DJ, Verdine GL (1997) A nonnatural transcriptional coactivator. Proc Natl Acad Sci USA 94(25):13402–13406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ojeda-Hernandez DD, Hernandez-Sapiens MA, Reza-Zaldivar EE, Canales-Aguirre A, Matias-Guiu JA, Matias-Guiu J, Mateos-Diaz JC, Gomez-Pinedo U, Sancho-Bielsa F (2022) Exosomes and biomaterials: in search of a new therapeutic strategy for multiple sclerosis. Life (basel) 12:9

    Google Scholar 

  • Okano H, Nakamura M, Yoshida K, Okada Y, Tsuji O, Nori S, Ikeda E, Yamanaka S, Miura K (2013) Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 112(3):523–533

    Article  CAS  PubMed  Google Scholar 

  • Ontaneda D, Tallantyre E, Kalincik T, Planchon SM, Evangelou N (2019) Early highly effective versus escalation treatment approaches in relapsing multiple sclerosis. Lancet Neurol 18(10):973–980

    Article  PubMed  Google Scholar 

  • Owens GM (2016) Economic burden of multiple sclerosis and the role of managed sare organizations in multiple sclerosis management. Am J Manag Care 22(6 Suppl):s151-158

    PubMed  Google Scholar 

  • Pan F, Zhang M, Wu G, Lai Y, Greber B, Scholer HR, Chi L (2013) Topographic effect on human induced pluripotent stem cells differentiation towards neuronal lineage. Biomaterials 34(33):8131–8139

    Article  CAS  PubMed  Google Scholar 

  • Panda B, Sharma Y, Gupta S, Mohanty S (2021) Mesenchymal stem cell-derived exosomes as an emerging paradigm for regenerative therapy and nano-medicine: a comprehensive review. Life (Basel) 11, 8

  • Papadimitriou C, Celikkaya H, Cosacak MI, Mashkaryan V, Bray L et al (2018) 3D culture method for Alzheimer's disease modeling reveals interleukin-4 rescues Abeta42-induced loss of human neural stem cell plasticity. Dev Cell 46(1): 85–101 e108

  • Park DJ, Yun WS, Kim WC, Park JE, Lee SH, Ha S, Choi JS, Key J, Seo YJ (2020) Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles. J Nanobiotechnol 18(1):178

    Article  CAS  Google Scholar 

  • Park JY, Kim SK, Woo DH, Lee EJ, Kim JH, Lee SH (2009) Differentiation of neural progenitor cells in a microfluidic chip-generated cytokine gradient. Stem Cells 27(11):2646–2654

    Article  CAS  PubMed  Google Scholar 

  • Park S, Im GI (2015) Stem cell responses to nanotopography. J Biomed Mater Res A 103(3):1238–1245

    Article  PubMed  Google Scholar 

  • Patel S, Jung D, Yin PT, Carlton P, Yamamoto M, Bando T, Sugiyama H, Lee KB (2014) NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation. ACS Nano 8(9):8959–8967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS (2018) Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol 16(1):71

    Article  PubMed  PubMed Central  Google Scholar 

  • Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760

    Article  CAS  PubMed  Google Scholar 

  • Pelaz B, Alexiou C, Alvarez-Puebla RA, Alves F, Andrews AM, Ashraf S, Balogh LP, Ballerini L, Bestetti A, Brendel C, Bosi S, Carril M, Chan WC, Chen C, Chen X, Chen X, Cheng Z, Cui D, Du J, Dullin C, Escudero A, Feliu N, Gao M, George M, Gogotsi Y, Grunweller A, Gu Z, Halas NJ, Hampp N, Hartmann RK, Hersam MC, Hunziker P, Jian J, Jiang X, Jungebluth P, Kadhiresan P, Kataoka K, Khademhosseini A, Kopecek J, Kotov NA, Krug HF, Lee DS, Lehr CM, Leong KW, Liang XJ, Ling Lim M, Liz-Marzan LM, Ma X, Macchiarini P, Meng H, Mohwald H, Mulvaney P, Nel AE, Nie S, Nordlander P, Okano T, Oliveira J, Park TH, Penner RM, Prato M, Puntes V, Rotello VM, Samarakoon A, Schaak RE, Shen Y, Sjoqvist S, Skirtach AG, Soliman MG, Stevens MM, Sung HW, Tang BZ, Tietze R, Udugama BN, VanEpps JS, Weil T, Weiss PS, Willner I, Wu Y, Yang L, Yue Z, Zhang Q, Zhang Q, Zhang XE, Zhao Y, Zhou X, Parak WJ (2017) Diverse applications of nanomedicine. ACS Nano 11(3):2313–2381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pende D, Falco M, Vitale M, Cantoni C, Vitale C, Munari E, Bertaina A, Moretta F, Del Zotto G, Pietra G, Mingari MC, Locatelli F, Moretta L (2019) Killer Ig-like Receptors (KIRs): their role in NK cell modulation and developments leading to their clinical exploitation. Front Immunol 10:1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petersen MA, Ryu JK, Chang KJ, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme CA, Wu MD, Coronado PER, Meyer-Franke A, Yahn S, Pous L, Lee JK, Schachtrup C, Lassmann H, Huang EJ, Han MH, Absinta M, Reich DS, Ellisman MH, Rowitch DH, Chan JR, Akassoglou K (2017) Fibrinogen activates BMP signaling in oligodendrocyte progenitor cells and inhibits remyelination after vascular damage. Neuron 96(5):1003–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, Cossetti C, Del Carro U (2009) Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol 66(3):343–354

    Article  CAS  PubMed  Google Scholar 

  • Price M, Lazzaro D, Pohl T, Mattei MG, Ruther U, Olivo JC, Duboule D, Di Lauro R (1992) Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain. Neuron 8(2):241–255

    Article  CAS  PubMed  Google Scholar 

  • Qi Y, Tan M, Hui CC, Qiu M (2003) Gli2 is required for normal Shh signaling and oligodendrocyte development in the spinal cord. Mol Cell Neurosci 23(3):440–450

    Article  CAS  PubMed  Google Scholar 

  • Qian Z, Li Y, Guan Z, Guo P, Zheng K, Du Y, Yin S, Chen B, Wang H, Jiang J, Qiu K, Zhang M (2023) Global, regional, and national burden of multiple sclerosis from 1990 to 2019: findings of global burden of disease study 2019. Front Public Health 11:1073278

    Article  PubMed  PubMed Central  Google Scholar 

  • Qiu M, Shimamura K, Sussel L, Chen S, Rubenstein JL (1998) Control of anteroposterior and dorsoventral domains of Nkx-6.1 gene expression relative to other Nkx genes during vertebrate CNS development. Mech Dev 72(1–2):77–88

    Article  CAS  PubMed  Google Scholar 

  • Qureshi AT, Monroe WT, Dasa V, Gimble JM, Hayes DJ (2013) miR-148b-nanoparticle conjugates for light mediated osteogenesis of human adipose stromal/stem cells. Biomaterials 34(31):7799–7810

    Article  CAS  PubMed  Google Scholar 

  • Rana N, Suliman S, Al-Sharabi N, Mustafa K (2022) Extracellular vesicles derived from primed mesenchymal stromal cells loaded on biphasic calcium phosphate biomaterial exhibit enhanced macrophage polarization. Cells 11:3

    Article  Google Scholar 

  • Ravanelli AM, Kearns CA, Powers RK, Wang Y, Hines JH, Donaldson MJ, Appel B (2018) Sequential specification of oligodendrocyte lineage cells by distinct levels of Hedgehog and Notch signaling. Dev Biol 444(2):93–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravichandran R, Sridhar R, Venugopal JR, Sundarrajan S, Mukherjee S, Ramakrishna S (2014) Gold nanoparticle loaded hybrid nanofibers for cardiogenic differentiation of stem cells for infarcted myocardium regeneration. Macromol Biosci 14(4):515–525

    Article  CAS  PubMed  Google Scholar 

  • Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Esfahani SH (2015) Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 4:53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reich DS, Lucchinetti CF, Calabresi PA (2018) Multiple sclerosis. N Engl J Med 378(2):169–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren M, Han Z, Li J, Feng G, Ouyang S (2015) Ascorbic acid delivered by mesoporous silica nanoparticles induces the differentiation of human embryonic stem cells into cardiomyocytes. Mater Sci Eng C Mater Biol Appl 56:348–355

    Article  CAS  PubMed  Google Scholar 

  • Reza-Zaldivar EE, Hernandez-Sapiens MA, Minjarez B, Gutierrez-Mercado YK, Marquez-Aguirre AL, Canales-Aguirre AA (2018) Potential effects of MSC-derived exosomes in neuroplasticity in Alzheimer’s disease. Front Cell Neurosci 12:317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riau AK, Ong HS, Yam GHF, Mehta JS (2019) Sustained delivery system for stem cell-derived exosomes. Front Pharmacol 10:1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riazifar M, Mohammadi MR, Pone EJ, Yeri A, Lasser C, Segaliny AI, McIntyre LL, Shelke GV, Hutchins E, Hamamoto A, Calle EN, Crescitelli R, Liao W, Pham V, Yin Y, Jayaraman J, Lakey JRT, Walsh CM, Van Keuren-Jensen K, Lotvall J, Zhao W (2019) Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano 13(6):6670–6688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riordan NH, Morales I, Fernandez G, Allen N, Fearnot NE, Leckrone ME, Markovich DJ, Mansfield D, Avila D, Patel AN, Kesari S, Paz Rodriguez J (2018) Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. J Transl Med 16(1):57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez Murua S, Farez MF, Quintana FJ (2022) The immune response in multiple sclerosis. Annu Rev Pathol 17:121–139

    Article  CAS  PubMed  Google Scholar 

  • Rowitch DH (2004) Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5(5):409–419

    Article  CAS  PubMed  Google Scholar 

  • Rudick RA, Cohen JA, Weinstock-Guttman B, Kinkel RP, Ransohoff RM (1997) Management of multiple sclerosis. N Engl J Med 337(22):1604–1611

    Article  CAS  PubMed  Google Scholar 

  • Rui K, Hong Y, Zhu Q, Shi X, Xiao F, Fu H, Yin Q, Xing Y, Wu X, Kong X, Xu H, Tian J, Wang S, Lu L (2021) Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjogren’s syndrome by modulating the function of myeloid-derived suppressor cells. Cell Mol Immunol 18(2):440–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan JM, Barry FP, Murphy JM, Mahon BP (2005) Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (lond) 2:8

    Article  PubMed  Google Scholar 

  • Sadhukha T, O’Brien TD, Prabha S (2014) Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release 196:243–251

    Article  CAS  PubMed  Google Scholar 

  • Sahoo S, Ang LT, Goh JC, Toh SL (2010) Growth factor delivery through electrospun nanofibers in scaffolds for tissue engineering applications. J Biomed Mater Res A 93(4):1539–1550

    Article  PubMed  Google Scholar 

  • Salehi Z, Hadiyan SP, Navidi R (2013) Ciliary neurotrophic factor role in myelin oligodendrocyte glycoprotein expression in Cuprizone-induced multiple sclerosis mice. Cell Mol Neurobiol 33(4):531–535

    Article  CAS  PubMed  Google Scholar 

  • Salunkhe S, Dheeraj M, Basak DC, Mittal A (2020) Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: Strategies and significance. J Control Release 326:599–614

    Article  CAS  PubMed  Google Scholar 

  • Samanta J, Grund EM, Silva HM, Lafaille JJ, Fishell G, Salzer JL (2015) Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination. Nature 526(7573):448–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandberg M, Flandin P, Silberberg S, Su-Feher L, Price JD, Hu JS, Kim C, Visel A, Nord AS, Rubenstein JLR (2016) Transcriptional networks controlled by NKX2-1 in the development of forebrain GABAergic neurons. Neuron 91(6):1260–1275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saraiva C, Praca C, Ferreira R, Santos T, Ferreira L, Bernardino L (2016) Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 235:34–47

    Article  CAS  PubMed  Google Scholar 

  • Sarathkumar E, Victor M, Menon JA, Jibin K, Padmini S, Jayasree RS (2021) Nanotechnology in cardiac stem cell therapy: cell modulation, imaging and gene delivery. RSC Adv 11(55):34572–34588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saulite L, Dapkute D, Pleiko K, Popena I, Steponkiene S, Rotomskis R, Riekstina U (2017) Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery. Beilstein J Nanotechnol 8:1218–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scolding NJ, Pasquini M, Reingold SC, Cohen JA et al (2017) Cell-based therapeutic strategies for multiple sclerosis. Brain 140(11):2776–2796

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen Z, Huang W, Liu J, Tian J, Wang S, Rui K (2021) Effects of mesenchymal stem cell-derived exosomes on autoimmune diseases. Front Immunol 12:749192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimamura K, Hartigan DJ, Martinez S, Puelles L, Rubenstein JL (1995) Longitudinal organization of the anterior neural plate and neural tube. Development 121(12):3923–3933

    Article  CAS  PubMed  Google Scholar 

  • Shin SR, Zihlmann C, Akbari M, Assawes P, Cheung L, Zhang K, Manoharan V, Zhang YS, Yuksekkaya M, Wan KT, Nikkhah M, Dokmeci MR, Tang XS, Khademhosseini A (2016) Reduced graphene oxide-GelMA hybrid hydrogels as scaffolds for cardiac tissue engineering. Small 12(27):3677–3689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shrivastava S, Dash DJJN (2009) Nanotechnology in agriculture. InTechOpen 184702:1–14

    Google Scholar 

  • Siegel G, Malmsten M, Ermilov E (2014) Anionic biopolyelectrolytes of the syndecan/perlecan superfamily: physicochemical properties and medical significance. Adv Colloid Interface Sci 205:275–318

    Article  CAS  PubMed  Google Scholar 

  • Silva GA, Czeisler C, Niece KL, Beniash E, Harrington DA, Kessler JA, Stupp SI (2004) Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 303(5662):1352–1355

    Article  CAS  PubMed  Google Scholar 

  • Silva ME, Lange S, Hinrichsen B, Philp AR, Reyes CR, Halabi D, Mansilla JB, Rotheneichner P, Guzman de la Fuente A, Couillard-Despres S, Batiz LF, Franklin RJM, Aigner L, Rivera FJ (2019) Pericytes favor oligodendrocyte fate choice in adult neural stem cells. Front Cell Neurosci 13:85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sniadecki NJ, Anguelouch A, Yang MT, Lamb CM, Liu Z, Kirschner SB, Liu Y, Reich DH, Chen CS (2007) Magnetic microposts as an approach to apply forces to living cells. Proc Natl Acad Sci USA 104(37):14553–14558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, Mancardi GL (2017) Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology 88(22):2115–2122

    Article  PubMed  Google Scholar 

  • Southwood C, He C, Garbern J, Kamholz J, Arroyo E, Gow A (2004) CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. J Neurosci 24(50):11215–11225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5(6):463–466

    Article  PubMed  PubMed Central  Google Scholar 

  • Stuermer EK, Lipenksy A, Thamm O, Neugebauer E, Schaefer N, Fuchs P, Bouillon B, Koenen P (2015) The role of SDF-1 in homing of human adipose-derived stem cells. Wound Repair Regen 23(1):82–89

    Article  PubMed  Google Scholar 

  • Sun T, Echelard Y, Lu R, Yuk DI, Kaing S, Stiles CD, Rowitch DH (2001) Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube. Curr Biol 11(18):1413–1420

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Villa-Diaz LG, Lam RH, Chen W, Krebsbach PH, Fu J (2012) Mechanics regulates fate decisions of human embryonic stem cells. PLoS ONE 7(5):e37178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Yong KM, Villa-Diaz LG, Zhang X, Chen W, Philson R, Weng S, Xu H, Krebsbach PH, Fu J (2014) Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells. Nat Mater 13(6):599–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szu J, Wojcinski A, Jiang P, Kesari S (2021) Impact of the olig family on neurodevelopmental disorders. Front Neurosci 15:659601

    Article  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Abarca LI, Muntion S, Preciado S, Puig N, Lopez-Ruano G, Hernandez-Hernandez A, Redondo A, Ortega R, Rodriguez C, Sanchez-Guijo F, del Canizo C (2016) MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun Signal 14:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Takata F, Nakagawa S, Matsumoto J, Dohgu S (2021) Blood-brain barrier dysfunction amplifies the development of neuroinflammation: understanding of cellular events in brain microvascular endothelial cells for prevention and treatment of BBB dysfunction. Front Cell Neurosci 15:661838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tarlinton RE, Khaibullin T, Granatov E, Martynova E, Rizvanov A, Khaiboullina S (2019) The interaction between viral and environmental risk factors in the pathogenesis of multiple sclerosis. Int J Mol Sci 20:2

    Article  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tian J, Zhu Q, Zhang Y, Bian Q, Hong Y, Shen Z, Xu H, Rui K, Yin K, Wang S (2020) Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate experimental colitis via modulating Th1/Th17 and treg cell responses. Front Immunol 11:598322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian T, Zhang HX, He CP, Fan S, Zhu YL, Qi C, Huang NP, Xiao ZD, Lu ZH, Tannous BA, Gao J (2018) Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials 150:137–149

    Article  CAS  PubMed  Google Scholar 

  • Treuel L, Brandholt S, Maffre P, Wiegele S, Shang L, Nienhaus GU (2014) Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions. ACS Nano 8(1):503–513

    Article  CAS  PubMed  Google Scholar 

  • Trinchieri G, Pflanz S, Kastelein RA (2003) The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 19(5):641–644

    Article  CAS  PubMed  Google Scholar 

  • Trounson A, McDonald C (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17(1):11–22

    Article  CAS  PubMed  Google Scholar 

  • Uccelli A, Laroni A, Freedman MS (2011) Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol 10(7):649–656

    Article  CAS  PubMed  Google Scholar 

  • Vallstedt A, Klos JM, Ericson J (2005) Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45(1):55–67

    Article  CAS  PubMed  Google Scholar 

  • Visweswaran M, Hendrawan K, Massey JC, Khoo ML, Ford CD, Zaunders JJ, Withers B, Sutton IJ, Ma DDF, Moore JJ (2022) Sustained immunotolerance in multiple sclerosis after stem cell transplant. Ann Clin Transl Neurol 9(2):206–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, LaRocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Napier CA, Rijke N, Baneke P (2020) Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler 26(14):1816–1821

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang GY, Rayner SL, Chung R, Shi BY, Liang XJ (2020a) Advances in nanotechnology-based strategies for the treatments of amyotrophic lateral sclerosis. Mater Today Bio 6:100055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Jelcic I, Muhlenbruch L, Haunerdinger V, Toussaint NC, Zhao Y, Cruciani C, Faigle W, Naghavian R, Foege M, Binder TMC, Eiermann T, Opitz L, Fuentes-Font L, Reynolds R, Kwok WW, Nguyen JT, Lee JH, Lutterotti A, Munz C, Rammensee HG, Hauri-Hohl M, Sospedra M, Stevanovic S, Martin R (2020b) HLA-DR15 molecules jointly shape an autoreactive T cell repertoire in multiple sclerosis. Cell 183(5):1264–1281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Yang L, Jiang M, Zhao C, Liu X, Berry K, Waisman A, Langseth AJ, Novitch BG, Bergles DE, Nishiyama A, Lu QR (2022a) Olig2 ablation in immature oligodendrocytes does not enhance CNS myelination and remyelination. J Neurosci 42(45):8542–8555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang JH, Thampatty BP (2008) Mechanobiology of adult and stem cells. Int Rev Cell Mol Biol 271:301–346

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Song F, Fernandez-Escobar A, Luo G, Wang JH, Sun Y (2018) The properties of cytokines in multiple sclerosis: pros and cons. Am J Med Sci 356(6):552–560

    Article  PubMed  Google Scholar 

  • Wang LC, Almazan G (2016) Role of sonic Hedgehog signaling in oligodendrocyte differentiation. Neurochem Res 41(12):3289–3299

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M, Goldman SA (2013) Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 12(2):252–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, Sdrulla AD, diSibio G, Bush G, Nofziger D, Hicks C, Weinmaster G, Barres BA (1998) Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21(1):63–75

    Article  PubMed  Google Scholar 

  • Wang Y, Cao Z, Wei Q, Ma K, Hu W, Huang Q, Su J, Li H, Zhang C, Fu X (2022b) VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1alpha-mediated enhancement of angiogenesis. Acta Biomater 147:342–355

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Li S, Ren X, Yu S, Meng X (2023) Nano-engineering nanomedicines with customized functions for tumor treatment applications. J Nanobiotechnol 21(1):250

    Article  Google Scholar 

  • Wegner M (2008) A matter of identity: transcriptional control in oligodendrocytes. J Mol Neurosci 35(1):3–12

    Article  CAS  PubMed  Google Scholar 

  • Wei M, Li S, Le W (2017) Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms. J Nanobiotechnol 15(1):75

    Article  Google Scholar 

  • Wen S, Li H, Liu J (2009) Dynamic signaling for neural stem cell fate determination. Cell Adh Migr 3(1):107–117

    Article  PubMed  PubMed Central  Google Scholar 

  • Wheeler MA, Clark IC, Tjon EC, Li Z, Zandee SEJ, Couturier CP, Watson BR, Scalisi G, Alkwai S, Rothhammer V, Rotem A, Heyman JA, Thaploo S, Sanmarco LM, Ragoussis J, Weitz DA, Petrecca K, Moffitt JR, Becher B, Antel JP, Prat A, Quintana FJ (2020) MAFG-driven astrocytes promote CNS inflammation. Nature 578(7796):593–599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler CC, Franco SJ (2019) Loss of Shh signaling in the neocortex reveals heterogeneous cell recovery responses from distinct oligodendrocyte populations. Dev Biol 452(1):55–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler CC, Yabut OR, Fregoso SP, Gomez HG, Dwyer BE, Pleasure SJ, Franco SJ (2018) The dorsal wave of neocortical oligodendrogenesis begins embryonically and requires multiple sources of sonic Hedgehog. J Neurosci 38(23):5237–5250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolinsky JS (1995) Copolymer 1: a most reasonable alternative therapy for early relapsing-remitting multiple sclerosis with mild disability. Neurology 45(7):1245–1247

    Article  CAS  PubMed  Google Scholar 

  • Xia Y, Sun J, Zhao L, Zhang F, Liang XJ, Guo Y, Weir MD, Reynolds MA, Gu N, Xu HHK (2018) Magnetic field and nano-scaffolds with stem cells to enhance bone regeneration. Biomaterials 183:151–170

    Article  CAS  PubMed  Google Scholar 

  • Xin Y, Gao J, Hu R, Li H, Li Q, Han F, He Z, Lai L, Su M (2020) Changes of immune parameters of T lymphocytes and macrophages in EAE mice after BM-MSCs transplantation. Immunol Lett 225:66–73

    Article  CAS  PubMed  Google Scholar 

  • Xinaris C, Morigi M, Benedetti V, Imberti B, Fabricio AS, Squarcina E, Benigni A, Gagliardini E, Remuzzi G (2013) A novel strategy to enhance mesenchymal stem cell migration capacity and promote tissue repair in an injury specific fashion. Cell Transpl 22(3):423–436

    Article  CAS  Google Scholar 

  • Yan X, Yang Y, Liu W, Geng W, Du H, Cui J, Xie X, Hua J, Yu S, Li L, Chen F (2013) Differentiation of neuron-like cells from mouse parthenogenetic embryonic stem cells. Neural Regen Res 8(4):293–300

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yao S, Li X, Liu J, Sun Y, Wang Z, Jiang Y (2017) Maximized nanodrug-loaded mesenchymal stem cells by a dual drug-loaded mode for the systemic treatment of metastatic lung cancer. Drug Deliv 24(1):1372–1383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye L, Swingen C, Zhang J (2013) Induced pluripotent stem cells and their potential for basic and clinical sciences. Curr Cardiol Rev 9(1):63–72

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yim EK, Pang SW, Leong KW (2007) Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp Cell Res 313(9):1820–1829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin T, Yang L, Liu Y, Zhou X, Sun J, Liu J (2015) Sialic acid (SA)-modified selenium nanoparticles coated with a high blood-brain barrier permeability peptide-B6 peptide for potential use in Alzheimer’s disease. Acta Biomater 25:172–183

    Article  CAS  PubMed  Google Scholar 

  • Yong VW, Chabot S, Stuve O, Williams G (1998) Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology 51(3):682–689

    Article  CAS  PubMed  Google Scholar 

  • Zafranskaya MM, Nizheharodova DB, Yurkevich MY, Lamouskaya NV, Motuzova YM, Bagatka SS, Ivanchik HI, Fedulov AS (2013) In vitro assessment of mesenchymal stem cells immunosuppressive potential in multiple sclerosis patients. Immunol Lett 149(1–2):9–18

    Article  CAS  PubMed  Google Scholar 

  • Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z (2019) Stem cells: past, present, and future. Stem Cell Res Ther 10(1):68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A (2005) Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 106(5):1755–1761

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Yan W, Zhu Y, Yang W, Le W, Chen B, Zhu R, Cheng L (2018a) Nanomaterials in neural-stem-cell-mediated regenerative medicine: imaging and treatment of neurological diseases. Adv Mater 30(17):e1705694

    Article  PubMed  Google Scholar 

  • Zhang B, Yeo RW, Tan KH, Lim SK (2016) Focus on extracellular vesicles: therapeutic potential of stem cell-derived extracellular vesicles. Int J Mol Sci 17(2):174

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Wang L, Li C, Yu Y, Yi Y, Wang J, Chen D (2019) Exosome-induced regulation in inflammatory bowel disease. Front Immunol 10:1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang K, Zhao X, Chen X, Wei Y, Du W, Wang Y, Liu L, Zhao W, Han Z, Kong D, Zhao Q, Guo Z, Han Z, Liu N, Ma F, Li Z (2018b) Enhanced therapeutic effects of mesenchymal stem cell-derived exosomes with an injectable hydrogel for hindlimb ischemia treatment. ACS Appl Mater Interfaces 10(36):30081–30091

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Satterlee A, Huang L (2012) In vivo gene delivery by nonviral vectors: overcoming hurdles? Mol Ther 20(7):1298–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L, Wang Q (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and being in white adipose tissue. Diabetes 67(2):235–247

    Article  CAS  PubMed  Google Scholar 

  • Zhou L, Shao CY, Xie YJ, Wang N, Xu SM, Luo BY, Wu ZY, Ke YH, Qiu M, Shen Y (2020) Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination. Elife 9:1

    Article  CAS  Google Scholar 

  • Zhou Q, Anderson DJ (2002) The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell 109(1):61–73

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Li X, Janairo RRR, Kwong G, Tsou AD, Chu JS, Wang A, Yu J, Wang D, Li S (2019) Matrix stiffness modulates the differentiation of neural crest stem cells in vivo. J Cell Physiol 234(5):7569–7578

    Article  CAS  PubMed  Google Scholar 

  • Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19(10):1769–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research has been supported by Science and Engineering Research Board, India (EEQ/2020/000188). BioRender software was used to create the figures appended in this manuscript.

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Authors and Affiliations

  1. Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences Central, University of Punjab, Bathinda, India

    Sushruta Ghosh & Jasvinder Singh Bhatti

  2. Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India

    Gurjit Kaur Bhatti

  3. Amity Institute of Biotechnology, Amity University, Rajasthan, India

    Pushpender Kumar Sharma

  4. Amity Centre for Nanobiotechnology and Nanomedicine, Amity University, Rajasthan, India

    Pushpender Kumar Sharma

  5. Department of Biochemistry, Kakatiya Medical College, Warangal, Telangana, India

    Ramesh Kandimalla

  6. Department of Applied Biology, CSIR-Indian Institute of Technology, Hyderabad, India

    Ramesh Kandimalla

  7. School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK

    Sarabjit Singh Mastana

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All authors have made substantial contributions to the following: SG, GKB, and JSB wrote the main manuscript text and PKS prepared Figs. 1, 2, 5, and 3. RK and SSM revise the article critically for important intellectual content. All authors reviewed the manuscript.

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Ghosh, S., Bhatti, G.K., Sharma, P.K. et al. Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review. Cell Mol Neurobiol 44, 6 (2024). https://doi.org/10.1007/s10571-023-01434-5

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