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Advances, Opportunities, and Challenges in Stem Cell-Based Therapy

  • Living reference work entry
  • First Online:
Handbook of Stem Cell Therapy

Abstract

In recent years, stem cell-based therapy is being widely and intensively investigated. Nowadays modern treatment strategies with mesenchymal stem cells (MSCs) in translational medicine are met with great enthusiasm by scientists and clinicians. The extraordinary properties of MSCs that are better known and understood mean that new possibilities of their application are constantly being tested. Due to their ability to self-regenerate, secrete biologically active molecules and exosomes, differentiate into several cell types, and participate in immunomodulation, MSCs have become a promising tool in the development of modern treatment strategies. The readily available and enormous potential of MSCs allows for a variety of clinical applications in the treatment of many diseases that have hitherto been called “incurable.” Most of the results of administering MSCs in clinical trials confirmed the safety and showed promising beneficial results. The therapeutic effects of MSC-based treatments are still not spectacular, and many features of MSCs have not yet been thoroughly investigated, so MSCs continue to be the source of controversial opinion and much debate about these cells. In this chapter, we focus on summarizing the current state of knowledge about the complex nature of MSCs that can be applied to regenerative medicine.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

AT-MSCs:

Adipose tissue-derived mesenchymal stem cells

BDNF:

Brain-derived neurotrophic factor

BM-MSCs:

Bone marrow-derived mesenchymal stem cells

CD:

Crohn’s disease

CFU-F:

Colony-forming unit–fibroblast

CMV:

Cytomegalovirus

EMA:

European Medicines Agency

EMT:

Epithelial-mesenchymal transition

ESCs:

Embryonic stem cells

EVs:

Extracellular vesicles

GvHD:

Graft versus host disease

HLA:

Human leukocyte antigens

HO:

Heterotopic ossification

HSCs:

Hematopoietic stem cells

HSCT:

Hematopoietic stem cell transplantation

IPSCs:

Induced pluripotent stem cells

ISCT:

International Society for Cellular Therapy

MNC:

Mononuclear cells

MPCs:

Mesenchymal progenitor cells

MSCs:

Mesenchymal stem cells

NGF:

Nerve growth factor

OA:

Osteoarthritis

OI:

Osteogenesis imperfecta

SSCs:

Somatic stem cells

WJ:

Wharton’s jelly

References

  • Afizah H, Zheng Yang Z, Hui JHP, Ouyang H-W, Lee E-H (2007) A comparison between the Chondrogenic potential of human Bone Marrow Stem Cells (BMSCs) and Adipose-Derived Stem Cells (ADSCs) taken from the same donors. Tissue Eng 13(4):659–666. https://doi.org/10.1089/ten.2006.0118

    Article  CAS  PubMed  Google Scholar 

  • Afzal MR, Haider KH, Niagara MI, Jiang S, Ahmed RPH, Ashraf M (2010) Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in infarcted heart via NF-кB signaling. Antioxid Redox Signal 12(6):693–702

    Article  CAS  Google Scholar 

  • Afzal MR, Samanta A, Shah ZI, Jeevanantham V, Abdel-Latif A, Zuba-Surma EK, Dawn B (2015) Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res. https://doi.org/10.1161/CIRCRESAHA.114.304792

  • Agarwal S, Drake J, Qureshi AT, Loder S, Li S, Shigemori K, Peterson J et al (2016) Characterization of cells isolated from genetic and trauma-induced heterotopic ossification. PLoS One. https://doi.org/10.1371/journal.pone.0156253

  • Agarwal S, Loder S, Cholok D, Li J, Breuler C, Drake J, Brownley C et al (2017) Surgical excision of heterotopic ossification leads to re-emergence of mesenchymal stem cell populations responsible for recurrence. Stem Cells Transl Med. https://doi.org/10.5966/sctm.2015-0365

  • Aguilera V, Briceño L, Contreras H, Lamperti L, Sepúlveda E, Díaz-Perez F, León M et al (2014) Endothelium trans differentiated from wharton’s jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors. PLoS One. https://doi.org/10.1371/journal.pone.0111025

  • Ahmed RPH, Haider KH, Shujia J, Afzal MR, Ashraf M (2010) Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway. PLoS One 5(1):e8576

    Article  Google Scholar 

  • Alvarez-Viejo M, Menendez-Menendez Y, Blanco-Gelaz MA, Ferrero-Gutierrez A, Fernandez-Rodriguez MA, Gala J, Otero-Hernandez J (2013) Quantifying mesenchymal stem cells in the mononuclear cell fraction of bone marrow samples obtained for cell therapy. Transplant Proc 45(1):434–439. https://doi.org/10.1016/j.transproceed.2012.05.091

    Article  CAS  PubMed  Google Scholar 

  • Anbari F, Khalili MA, Bahrami AR, Khoradmehr A, Sadeghian F, Fesahat F, Nabi A (2014) Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury. Neural Regen Res. https://doi.org/10.4103/1673-5374.133133

  • Argibay B, Trekker J, Himmelreich U, Beiras A, Topete A, Taboada P, Pérez-Mato M et al (2017) Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia. Sci Rep. https://doi.org/10.1038/srep40758

  • Badillo AT, Peranteau WH, Heaton TE, Quinn C, Flake AW (2008) Murine bone marrow derived stromal progenitor cells fail to prevent or treat acute graft-versus-host disease. Br J Haematol. https://doi.org/10.1111/j.1365-2141.2008.07040.x

  • Balan A, Lucchini G, Schmidt S, Schneider A, Tramsen L, Kuçi S, Meisel R et al (2014) Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease – friends or foes. Leukemia

    Google Scholar 

  • Batsali KA, Kastrinaki M-C, Papadaki HA, Pontikoglou C (2013) Mesenchymal stem cells derived from Wharton’s jelly of the umbilical cord: biological properties and emerging clinical applications. Curr Stem Cell Res Ther. https://doi.org/10.2174/1574888x11308020005

  • Belostotskaya G, Nevorotin A, Galagudza M (2015) Identification of cardiac stem cells within mature cardiac myocytes. Cell Cycle 14(19):3155–3162. https://doi.org/10.1080/15384101.2015.1078037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berebichez-Fridman R, Gómez-García R, Granados-Montiel J, Berebichez-Fastlicht E, Olivos-Meza A, Granados J, Velasquillo C et al (2017) The holy grail of Orthopedic surgery: mesenchymal stem cells – their current uses and potential applications. Stem Cells Int 2017(2017):2638305. https://doi.org/10.1155/2017/2638305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D et al (2007) Human bone marrow-derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-06-4690

  • Breitbach M, Bostani T, Roell W, Xia Y, Dewald O, Nygren JM, JWU F et al (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood. https://doi.org/10.1182/blood-2006-12-063412

  • Buccini S, Haider KH, Ahmed RPH, Jiang S, Ashraf M (2012) Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. Basic Res Cardiol 107(6):301

    Article  Google Scholar 

  • Changfa G, Zhu K, Haider KH (2017) Nanoparticle based genetic engineering of mesenchymal stem cells. In: Haider KH (ed) Stem cells: from drug to drug discovery, Medicine & life sciences. De Gruyter, Berlin

    Google Scholar 

  • Ciccocioppo R, Comoli P, Astori G, del Bufalo F, Prapa M, Dominici M, Locatelli F (2021) Developing cell therapies as drug products. Br J Pharmacol

    Google Scholar 

  • Contentin R, Demoor M, Concari M, Desancé M, Audigié F, Branly T, Galéra P (2020) Comparison of the chondrogenic potential of mesenchymal stem cells derived from bone marrow and umbilical cord blood intended for cartilage tissue engineering. Stem Cell Rev Rep 16(1):126–143. https://doi.org/10.1007/s12015-019-09914-2

    Article  CAS  PubMed  Google Scholar 

  • Crippa S, Bernardo ME (2018) Mesenchymal stromal cells: role in the BM Niche and in the support of Hematopoieitic stem cell transplantation. HemaSphere 2(6):e151. https://doi.org/10.1097/HS9.0000000000000151

    Article  PubMed  PubMed Central  Google Scholar 

  • Cui LL, Kinnunen T, Boltze J, Nystedt J, Jolkkonen J (2016) Clumping and viability of bone marrow derived mesenchymal stromal cells under different preparation procedures: a flow cytometry-based in vitro study. Stem Cells Int. https://doi.org/10.1155/2016/1764938

  • D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA (1999) Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res. https://doi.org/10.1359/jbmr.1999.14.7.1115

  • da Silva ML (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. https://doi.org/10.1242/jcs.02932

  • Dawn B, Abdel-Latif A, Sanganalmath SK, Flaherty MP, Zuba-surma EK (2009) Cardiac repair with adult bone marrow-derived cells: the clinical evidence. Antioxidants Redox Signal

    Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS, Deans RJ et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. https://doi.org/10.1080/14653240600855905

  • Elgaz S, Kuçi Z, Kuçi S, Bönig H, Bader P (2019) Clinical use of mesenchymal stromal cells in the treatment of acute graft-versus-host disease. Transfus Med Hemother 46:27–34. https://doi.org/10.1159/000496809

    Article  PubMed  PubMed Central  Google Scholar 

  • Filardo G, Perdisa F, Roffi A, Marcacci M, Kon E (2016) Stem cells in articular cartilage regeneration. J Orthop Surg Res. https://doi.org/10.1186/s13018-016-0378-x

  • Forbes GM, Sturm MJ, Leong RW, Sparrow MP, Segarajasingam D, Cummins AG, Phillips M et al (2014) A phase 2 study of allogeneic mesenchymal stromal cells for luminal crohn’s disease refractory to biologic therapy. Clin Gastroenterol Hepatol. https://doi.org/10.1016/j.cgh.2013.06.021

  • Forslöw U, Blennow O, Leblanc K, Ringdén O, Gustafsson B, Mattsson J, Remberger M (2012) Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation. Eur J Haematol. https://doi.org/10.1111/j.1600-0609.2012.01824.x

  • Fraser JK, Wulur I, Alfonso Z, Hedrick MH (2006) Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2006.01.010

  • Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of Guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Gorskaja UF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4:267–274

    CAS  PubMed  Google Scholar 

  • Fujimura J, Sugihara H, Fukunaga Y, Suzuki H, Ogawa R (2009) Adipose tissue is a better source of immature non-hematopoietic cells than bone marrow. Int J Stem Cells. https://doi.org/10.15283/ijsc.2009.2.2.135

  • Gálvez P, Ruiz A, Clares B (2011) The future of new therapies in clinical medicine. Med Clin (Barc)

    Google Scholar 

  • Gálvez P, Clares B, Hmadcha A, Ruiz A, Soria B (2013) Development of a cell-based medicinal product: regulatory structures in the European Union. Br Med Bull. https://doi.org/10.1093/bmb/lds036

  • Ge J, Guo L, Wang S, Zhang Y, Cai T, Zhao RCH, Wu Y (2014) The size of mesenchymal stem cells is a significant cause of vascular obstructions and stroke. Stem Cell Rev Reports. https://doi.org/10.1007/s12015-013-9492-x

  • Ghaemi SR, Harding FJ, Delalat B, Gronthos S, Voelcker NH (2013) Exploring the mesenchymal stem cell niche using high throughput screening. Biomaterials 34(31):7601–7615. https://doi.org/10.1016/j.biomaterials.2013.06.022

    Article  CAS  PubMed  Google Scholar 

  • Gisbert JP, Marín AC, Chaparro M (2015) Systematic review: factors associated with relapse of inflammatory bowel disease after discontinuation of anti-TNF therapy. Aliment Pharmacol Ther 42(4):391–405. https://doi.org/10.1111/apt.13276

    Article  CAS  PubMed  Google Scholar 

  • Gordon T (2009) The role of neurotrophic factors in nerve regeneration. Neurosurg Focus. https://doi.org/10.3171/FOC.2009.26.2.E3

  • Gornicka-Pawlak E, Janowski M, Habich A, Jablonska A, Drela K, Kozlowska H, Lukomska B et al (2011) Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment. Acta Neurobiol Exp (Wars)

    Google Scholar 

  • Götherström C, Westgren M, Shaw SWS, Åström E, Biswas A, Byers PH, Mattar CNZ et al (2014) Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Transl Med. https://doi.org/10.5966/sctm.2013-0090

  • Gu N, Rao C, Tian Y, Di Z, Liu Z, Chang M, Lei H (2014) Anti-inflammatory and antiapoptotic effects of mesenchymal stem cells transplantation in rat brain with cerebral ischemia. J Stroke Cerebrovasc Dis. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.05.032

  • Guillot PV, Gotherstrom C, Chan J, Kurata H, Fisk NM (2007) Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells. https://doi.org/10.1634/stemcells.2006-0208

  • Haider KH (2006) Bone marrow cells for cardiac regeneration and repair: current status and issues. Expert Rev Cardiovasc Ther 4:557–568

    Article  CAS  Google Scholar 

  • Haider KH (2018) The aging stem cells and cardiac reparability: lesson learnt from clinical studies is that old is not always gold. Regen Med 13(4):457–475

    Article  CAS  Google Scholar 

  • Haider KH, Aramini B (2020) Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy. Stem Cell Res Ther 11(1):23. https://doi.org/10.1186/s13287-019-1548-7

    Article  PubMed  PubMed Central  Google Scholar 

  • Haider KH, Ashraf M (2005) Bone marrow cell transplantation in clinical perspective. J Mol Cell Cardiol 38:225–235

    Article  CAS  Google Scholar 

  • Haider KH, Aslam M (2018) Cell-free therapy with stem cell secretions: Protection, repair and regeneration of the injured myocardium. In: Haider KH, Aziz S (eds) Stem cells: from hype to real hope, Medicine & life sciences. De Gruyter, Berlin

    Google Scholar 

  • Haider KH, Aziz S (2017) Paracrine hypothesis and cardiac repair. Int J Stem Cell Res Transplant 5(1):265–267

    Google Scholar 

  • Haider KH, Tan T, Aziz S, Chachques JC, Sim EKW (2004) Myoblast transplantation for cardiac repair: a clinical perspective. Mol Ther 9:14–23

    Article  CAS  Google Scholar 

  • Haider KH, Jiang S, Niagara MI (2008) Ashraf M (2008) IGF-I over expressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circulation Res 103:1300–1308

    Article  CAS  Google Scholar 

  • Haider KH, Lee YJ, Jiang S, Ahmed RPH, Ryon M, Ashraf M (2010) Phosphodiesterase inhibition with tadalafil provides longer and sustained protection of stem cells. Am J Physiol Heart Circul Physiol 299(5):H1395–H1404

    Article  CAS  Google Scholar 

  • Halfon S, Abramov N, Grinblat B, Ginis I (2011) Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev. https://doi.org/10.1089/scd.2010.0040

  • Hass R, Kasper C, Böhm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal

    Google Scholar 

  • Horwitz EM, Gordon PL, Koo WKK, Marx JC, Neel MD, McNall RY, Muul L et al (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.132252399

  • Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ et al (2005) Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy. https://doi.org/10.1080/14653240500319234

  • Hosseini SM, Sani M, Haider KH, Dorvash MR, Ziaee SM, Karimi A (2018) Concomitant use of mesenchymal stem cells and neural stem cells for treatment of spinal cord injury: a combo cell therapy approach. Neurosci Lett 668:138–146

    Article  CAS  Google Scholar 

  • Im G Il, Shin YW, Lee KB (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthr Cartil. https://doi.org/10.1016/j.joca.2005.05.005

  • Jiang S, Haider KH, Niagara MI, Lu G, Ashraf M (2008) Stable therapeutic effects of mesenchymal stem cell based multiple gene delivery for cardiac repair. Cardiovasc Res 77(3):525–533

    Google Scholar 

  • Jihwan HJ, Alice RY, Yoojun N, Hyeon JJ (2021) Recent developments in clinical applications of mesenchymal stem cells in the treatment of rheumatoid arthritis and osteoarthritis. Front Immunol 12:448. https://doi.org/10.3389/fimmu.2021.631291

    Article  CAS  Google Scholar 

  • Kahn J (2006) Myoblast cell therapy shows promise, but safety issues linger. J Interv Cardiol

    Google Scholar 

  • Kan C, Chen L, Hu Y, Lu H, Li Y, Kessler JA, Kan L (2017) Microenvironmental factors that regulate mesenchymal stem cells: lessons learned from the study of heterotopic ossification. Histol Histopathol

    Google Scholar 

  • Karlsson H, Samarasinghe S, Ball LM, Sundberg B, Lankester AC, Dazzi F, Uzunel M et al (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood. https://doi.org/10.1182/blood-2007-10-119370

  • Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JWM et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. https://doi.org/10.1001/archneurol.2010.248

  • Kim HW, Haider KH, Jiang S, Ashraf M (2009) Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem 284(48):33161–33168

    Article  Google Scholar 

  • Kingery MT, Manjunath AK, Anil U, Strauss EJ (2019) Bone marrow mesenchymal stem cell therapy and related bone marrow-derived orthobiologic therapeutics. Curr Rev Musculoskelet Med 12(4):451–459. https://doi.org/10.1007/s12178-019-09583-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Kitagawa Y, Kobori M, Toriyama K, Kamei Y, Torii S (2006) History of discovery of human adipose-derived stem cells and their clinical application. Japanese J Plast Reconstr Surg

    Google Scholar 

  • Kundrotas G (2012) Surface markers distinguishing mesenchymal stem cells from fibroblasts. Acta Med Litu. https://doi.org/10.6001/actamedica.v19i2.2313

  • Kuroda Y, Kitada M, Wakao S, Nishikawa K, Tanimura Y, Makinoshima H, Goda M et al (2010) Unique multipotent cells in adult human mesenchymal cell populations. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.0911647107

  • Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Nuñez-Córdoba JM, Sánchez-Echenique C et al (2016) Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med. https://doi.org/10.1186/s12967-016-0998-2

  • Le Blanc K, Mougiakakos D (2012) Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol

    Google Scholar 

  • Lei Y, Haider KH (2017) “Paracrining” the heart with stem cells. In: Haider KH (ed) Stem cells: from drug to drug discovery, Medicine & life sciences. De Gruyter, Berlin

    Google Scholar 

  • Li Y, Altemus J, Lightner AL (2020) Mesenchymal stem cells and acellular products attenuate murine induced colitis. Stem Cell Res Ther 11:515. https://doi.org/10.1186/s13287-020-02025-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin CS, Xin ZC, Dai J, Lue TF (2013) Commonly used mesenchymal stem cell markers and tracking labels: limitations and challenges. Histol Histopathol

    Google Scholar 

  • Lindenmair A, Hatlapatka T, Kollwig G, Hennerbichler S, Gabriel C, Wolbank S, Redl H et al (2012) Mesenchymal stem or stromal cells from amnion and umbilical cord tissue and their potential for clinical applications. Cell. https://doi.org/10.3390/cells1041061

  • Ljujic B, Milovanovic M, Volarevic V, Murray B, Bugarski D, Przyborski S, Arsenijevic N et al (2013) Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice. Sci Rep. https://doi.org/10.1038/srep02298

  • Lpez Y, Lutjemeier B, Seshareddy KM, Trevino E, Sue Hageman K, Musch T, Borgarelli M, Weiss M (2013) Wharton’s Jelly or bone marrow mesenchymal stromal cells improve cardiac function following myocardial infarction for more than 32 weeks in a rat model: a preliminary report. Curr Stem Cell Res Ther. https://doi.org/10.2174/1574888x11308010007

  • Lu L, Li F, Lu J (2013) Identification of functional tissue-resident cardiac stem/progenitor cells in adult mouse. Cell Biol Int Rep 19(1):15–22. https://doi.org/10.1042/CBR20120001

    Article  Google Scholar 

  • Lupatov AY, Vdovin AS, Vakhrushev IV, Poltavtseva RA, Yarygin KN (2015) Comparative analysis of the expression of surface markers on fibroblasts and fibroblast-like cells isolated from different human tissues. Bull Exp Biol Med. https://doi.org/10.1007/s10517-015-2803-2

  • Lv FJ, Tuan RS, Cheung KMC, Leung VYL (2014) Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells

    Google Scholar 

  • Lykissas M, Batistatou A, Charalabopoulos K, Beris A (2007) The role of neurotrophins in axonal growth, guidance, and regeneration. Curr Neurovasc Res. https://doi.org/10.2174/156720207780637216

  • Machaliński B, Łazewski-Banaszak P, Dabkowska E, Paczkowska E, Gołab-Janowska M, Nowacki P (2012) The role of neurotrophic factors in regeneration of the nervous system. Neurol Neurochir Pol

    Google Scholar 

  • Majka M, Sułkowski M, Badyra B, Musiałek P (2017) Concise review: mesenchymal stem cells in cardiovascular regeneration: emerging research directions and clinical applications. Stem Cells Transl Med

    Google Scholar 

  • Maleki M, Ghanbarvand F, Behvarz MR, Ejtemaei M, Ghadirkhomi E (2014) Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells. https://doi.org/10.15283/ijsc.2014.7.2.118

  • Malgieri A, Kantzari E, Patrizi MP, Gambardella S (2010) Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med

    Google Scholar 

  • Marcucio RS, Nauth A, Giannoudis PV, Bahney C, Piuzzi NS, Muschler G, Miclau T (2015) Stem cell therapies in orthopaedic trauma. J Orthop Trauma. https://doi.org/10.1097/BOT.0000000000000459

  • Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, Litzow MR et al (2012) First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant

    Google Scholar 

  • Menasché P (2009) Stem cell therapy for heart failure. Are arrhythmias a real safety concern? Circulation 119:2735–2740. https://doi.org/10.1161/CIRCULATIONAHA.108.812693

    Article  PubMed  Google Scholar 

  • Miura M, Miura Y, Padilla-Nash HM, Molinolo AA, Fu B, Patel V, Seo B-M et al (2006) Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells. https://doi.org/10.1634/stemcells.2005-0403

  • Mohanty A, Polisetti N, Vemuganti GK (2020) Immunomodulatory properties of bone marrow mesenchymal stem cells. J Biosci 45:98. https://doi.org/10.1007/s12038-020-00068-9

    Article  PubMed  Google Scholar 

  • Moniuszko A, Sarnowska A, Rogowski W, Durlik M, Wluka A, Rydzewska G (2018) Successful treatment of an enterovesical fistula due to Crohn’s disease with stem cell transplantation: a case report. Prz Gastroenterol

    Google Scholar 

  • Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C (2010) Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Adv Biochem Eng Biotechnol. https://doi.org/10.1007/10_2009_15

  • Muroi K, Miyamura K, Okada M, Yamashita T, Murata M, Ishikawa T, Uike N et al (2016) Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study. Int J Hematol. https://doi.org/10.1007/s12185-015-1915-9

  • Murrell WD, Anz AW, Badsha H, Bennett WF, Boykin RE, Caplan AI (2015) Regenerative treatments to enhance Orthopedic surgical outcome. PM & R 7(4):S41–S52. https://doi.org/10.1016/j.pmrj.2015.01.015

    Article  Google Scholar 

  • Musiał-Wysocka A, Kot M, Sułkowski M, Badyra B, Majka M (2019) Molecular and functional verification of wharton’s jelly mesenchymal stem cells (WJ-MSCs) pluripotency. Int J Mol Sci. https://doi.org/10.3390/ijms20081807

  • Nagamura-Inoue T (2014) Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J Stem Cells. https://doi.org/10.4252/wjsc.v6.i2.195

  • Nauta AJ, Fibbe WE (2007) Immunomodulatory properties of mesenchymal stromal cells. Blood

    Google Scholar 

  • Nazari-Shafti TZ, Neuber S, Garcia Duran A, Xu Z, Beltsios E, Seifert M, Falk V et al (2020) Human mesenchymal stromal cells and derived extracellular vesicles: translational strategies to increase their proangiogenic potential for the treatment of cardiovascular disease. Stem Cells Transl Med. https://doi.org/10.1002/sctm.19-0432

  • Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia. https://doi.org/10.1038/sj.leu.2405090

  • Ocansey DKW, Zhang L, Wang Y, Yan Y, Qian H, Zhang X, Xu W et al (2020) Exosome-mediated effects and applications in inflammatory bowel disease. Biol Rev 95(5):1287–1307

    Article  Google Scholar 

  • Ogura F, Wakao S, Kuroda Y, Tsuchiyama K, Bagheri M, Heneidi S, Chazenbalk G et al (2014) Human adipose tissue possesses a unique population of pluripotent stem cells with nontumorigenic and low telomerase activities: potential implications in regenerative medicine. Stem Cells Dev. https://doi.org/10.1089/scd.2013.0473

  • Oh K-W, Moon C, Kim HY, Oh S, Park J, Lee JH, Chang IY et al (2015) Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. https://doi.org/10.5966/sctm.2014-0212

  • Okada M, Haider KH, Kim S, Ashraf M (2011) Existence of small juvenile cells in the aging bone marrow stromal cells and their therapeutic potential for ischemic heart disease. Circulation, Nov. 2011-SS-A-9586-AHA

    Google Scholar 

  • Paczkowska E, Kaczyńska K, Pius-Sadowska E, Rogińska D, Kawa M, Ustianowski P, Safranow K et al (2013) Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders. PLoS One. https://doi.org/10.1371/journal.pone.0083833

  • Paczkowska E, Rogińska D, Pius-Sadowska E, Jurewicz A, Piecyk K, Safranow K, Dziedziejko V et al (2015) Evidence for proangiogenic cellular and humoral systemic response in patients with acute onset of spinal cord injury. J Spinal Cord Med. https://doi.org/10.1179/2045772314Y.0000000227

  • Park Y-B, Ha C-W, Lee C-H, Yoon YC, Park Y-G (2016) Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med. https://doi.org/10.5966/sctm.2016-0157

  • Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH (2017) Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med

    Google Scholar 

  • Pelosi E, Castelli G, Testa U (2012) Human umbilical cord is a unique and safe source of various types of stem cells suitable for treatment of hematological diseases and for regenerative medicine. Blood Cells Mol Dis

    Google Scholar 

  • Peng X, Zhou J, Wu X (2016) New strategies for myocardial infarction treatment. J Cardiol Ther 4(3):664–670

    Article  Google Scholar 

  • Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A et al (2016) Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis. JAMA Neurol https://doi.org/10.1001/jamaneurol.2015.4321

  • Pevsner-Fischer M, Levin S, Zipori D (2011) The origins of mesenchymal stromal cell heterogeneity. Stem Cell Rev Rep

    Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147. https://doi.org/10.1126/science.284.5411.143

    Article  CAS  PubMed  Google Scholar 

  • Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, Shah PK et al (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol. https://doi.org/10.1016/j.ijcard.2005.07.036

  • Ratajczak MZ, Suszyńska M (2013) Quo Vadis medycyno regeneracyjna? Acta Haematol Pol 44:161–170 . https://doi.org/10.1016/j.achaem.2013.07.023

  • Ratajczak MZ (2017) Quo Vadis regenerative medicine? Eur J Oncol Pharm

    Google Scholar 

  • Ringden O, Baygan A, Remberger M, Gustafsson B, Winiarski J, Khoein B, Moll G et al (2018) Placenta-derived decidua stromal cells for treatment of severe acute graft-versus-host disease. Stem Cells Transl Med. https://doi.org/10.1002/sctm.17-0167

  • Sadan O, Shemesh N, Barzilay R, Dadon-Nahum M, Blumenfeld-Katzir T, Assaf Y, Yeshurun M et al (2012) Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: a potential therapy for Huntington’s disease. Exp Neurol. https://doi.org/10.1016/j.expneurol.2011.12.045

  • Sancricca C (2010) Mesenchymal stromal cells from human perinatal tissues: from biology to cell therapy. World J Stem Cells. https://doi.org/10.4252/wjsc.v2.i4.81

  • Sarnowska A, Jablonska A, Jurga M, Dainiak M, Strojek L, Drela K, Wright K et al (2013) Encapsulation of mesenchymal stem cells by bioscaffolds protects cell survival and attenuates neuroinflammatory reaction in injured brain tissue after transplantation. Cell Transplant. https://doi.org/10.3727/096368913X672172

  • Shahid MS, Lasheen W, Haider KH (2016) Modest outcome of clinical trials with bone marrow cells for myocardial repair: is the autologous source of cells the prime culprit? J Thorac Dis 8(10):E1371–E1374

    Article  Google Scholar 

  • Shim WSN, Jiang S, Wong P, Tan J, Chua YL, Seng Tan Y, Sin YK et al (2004) Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2004.09.087

  • Shim G, Lee S, Han J, Kim G, Jin H, Miao W, Yi TG et al (2015) Pharmacokinetics and in vivo fate of intra-articularly transplanted human bone marrow-derived clonal mesenchymal stem cells. Stem Cells Dev. https://doi.org/10.1089/scd.2014.0240

  • Shimomura K, Ando W, Fujie H, Hart DA, Yoshikawa H, Nakamura N (2018) Scaffold-free tissue engineering for injured joint surface restoration. J Exp Orthop

    Google Scholar 

  • Siegel G, Kluba T, Hermanutz-Klein U, Bieback K, Northoff H, Schäfer R (2013) Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells. BMC Med. https://doi.org/10.1186/1741-7015-11-146

  • Staffe NP, Madigan NN, Morris J, Jentoft M, Sorenson EJ, Butler G, Gastineau D et al (2016) Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology. https://doi.org/10.1212/WNL.0000000000003359

  • Steiner B, Roch M, Holtkamp N, Kurtz A (2012) Systemically administered human bone marrow-derived mesenchymal stem home into peripheral organs but do not induce neuroprotective effects in the MCAo-mouse model for cerebral ischemia. Neurosci Lett. https://doi.org/10.1016/j.neulet.2012.01.078

  • Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. https://doi.org/10.1016/j.mad.2007.12.002

  • Suzuki Y, Kim HW, Ashraf M, Haider KH (2010) Diazoxide potentiates mesenchymal stem cell survival via NF-κB-dependent miR-146a expression. Am J Phys 299:H1077–H1082

    CAS  Google Scholar 

  • Syková E, Rychmach P, Drahorádová I, Konrádová Š, Růžičková K, Voříšek I, Forostyak S et al (2017) Transplantation of mesenchymal stromal cells in patients with amyotrophic lateral sclerosis: results of phase I/IIa clinical trial. Cell Transplant. https://doi.org/10.3727/096368916X693716

  • Szydlak R (2019) Mesenchymal stem cells’ homing and cardiac tissue repair. Acta Biochim Pol 66:483–489. https://doi.org/10.18388/ABP.2019_2890

    Article  CAS  PubMed  Google Scholar 

  • Taei AA, Nasoohi S, Hassanzadeh G, Kadivar M, Dargahi L, Farahmandfar M (2021) Enhancement of angiogenesis and neurogenesis by intracerebroventricular injection of secretome from human embryonic stem cell-derived mesenchymal stem cells in ischemic stroke model. Biomed Pharmacother 140:111709. https://doi.org/10.1016/j.biopha.2021.111709

    Article  CAS  Google Scholar 

  • Takamiya M, Haider KH, Ashraf M (2011) Identification and characterization of a novel multipotent sub-population of sca-1+ cardiac progenitor cells for myocardial regeneration. PLoS One 6(9):e25265

    Article  CAS  Google Scholar 

  • Tang Q, Chen Q, Lai X, Liu S, Chen Y, Zheng Z, Xie Q et al (2013) Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction. PLoS One. https://doi.org/10.1371/journal.pone.0081844

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

    Google Scholar 

  • Veauthier B, Hornecker JR (2018) Crohn’s disease: diagnosis and management. Am Fam Physician 98(11):661–669

    PubMed  Google Scholar 

  • Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM et al (2020) Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation

    Google Scholar 

  • Viswanathan S, Shi Y, Galipeau J, Krampera M, Leblanc K, Martin I, Nolta J et al (2019) Mesenchymal stem versus stromal cells: International Society for Cellular Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. https://doi.org/10.1016/j.jcyt.2019.08.002

  • Von Bahr L, Batsis I, Moll G, Hägg M, Szakos A, Sundberg B, Uzunel M et al (2012a) Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells. https://doi.org/10.1002/stem.1118

  • von Bahr L, Sundberg B, Lönnies L, Sander B, Karbach H, Hägglund H, Ljungman P et al (2012b) Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant. https://doi.org/10.1016/j.bbmt.2011.07.023

  • Wang M, Yuan Q, Xie L (2018) Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int

    Google Scholar 

  • Weng JY, Du X, Geng SX, Peng YW, Wang Z, Lu ZS, Wu SJ et al (2010) Mesenchymal stem cell as salvage treatment for refractory chronic GVHD. Bone Marrow Transplant. https://doi.org/10.1038/bmt.2010.195

  • Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM (2003) Adult bone marrow is a rich source of human mesenchymal “stem” cells but umbilical cord and mobilized adult blood are not. Br J Haematol. https://doi.org/10.1046/j.1365-2141.2003.04284.x

  • White JL, Walker NJ, Hu JC, Borjesson DL, Athanasiou KA (2018) A comparison of bone marrow and cord blood mesenchymal stem cells for cartilage self-assembly. Tissue Eng Part A. https://doi.org/10.1089/ten.tea.2017.0424

  • Winkler S, Niedermair T, Füchtmeier B, Grifka J, Grässel S, Anders S, Heers G et al (2015) The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification. Int Orthop. https://doi.org/10.1007/s00264-015-2995-0

  • Xu-ting W, Bian-yu Z, Fan-ming Q, Li G, Tang-ting T (2009) Human mesenchymal stem cells (hMSCs) target osteosarcoma and promote its growth and pulmonary metastasis. Cancer Lett. https://doi.org/10.1016/j.canlet.2009.02.022

  • Yang HJ, Kim K-J, Kim MK, Lee SJ, Ryu YH, Seo BF, Oh D-Y (2014) The stem cell potential and multipotency of human adipose tissue-derived stem cells vary by cell donor and are different from those of other types of stem cells. Cells Tissues Organs 199:373–383. https://doi.org/10.1159/000369969

    Article  PubMed  Google Scholar 

  • Yin F, Guo L, Meng CY, Liu YJ, Lu RF, Li P, Zhou YB (2014) Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury. Brain Res. https://doi.org/10.1016/j.brainres.2014.02.047

  • Zeddou M, Briquet A, Relic B, Josse C, Malaise MG, Gothot A, Lechanteur C et al (2010) The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell Biol Int. https://doi.org/10.1042/cbi20090414

  • Zhang XM, Zhang YJ, Wang W, Wei YQ, Deng HX (2017) Mesenchymal stem cells to treat Crohn’s disease with fistula. Hum Gene Ther

    Google Scholar 

  • Zhao K, Lou R, Huang F, Peng Y, Jiang Z, Huang K, Wu X et al (2015) Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. https://doi.org/10.1016/j.bbmt.2014.09.030

  • Zimmerlin L, Donnenberg AD, Rubin JP, Basse P, Landreneau RJ, Donnenberg VS (2011) Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue Eng Part A. https://doi.org/10.1089/ten.tea.2010.0248

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Acknowledgments

This work was supported by a research grant (STRATEGMED2/265761/10/NCBR/2015) from the National Center for Research and Development in Poland.

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  1. Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland

    Renata Szydlak

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  1. Renata Szydlak
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  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

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  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

  2. University of Modena and Reggio Emilia, Modena, Italy

    Beatrice Aramini

  3. Interamerican Open University, Buenos Aires, Argentina

    Elio A. Prieto Gonzalez

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Szydlak, R. (2022). Advances, Opportunities, and Challenges in Stem Cell-Based Therapy. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_23-1

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