Abstract
The discovery of extracellular vesicles has provided an outstanding breakthrough in stem cells and regenerative medicine. It has been shown that cells can transfer information through the secretion of soluble factors, the formation of direct physical contacts, and the secretion of extracellular vesicles containing a wide range of biologically active factors, including proteins, lipids, and genetic information. All these factors are protected from destruction by the extracellular vesicles’ bilayer lipid membrane, allowing the transfer of information from cell to cell over considerable distances. Extracellular vesicles derived from stem cells can reprogram a range of target cells, stimulating their viability and migration. The biological capacity and regenerative potential of stem cell-derived extracellular vesicles are comparable to that of the stem cells in vivo. Due to biosafety concerns over the use of cell-based therapies, the potential of a cell-free therapy based on extracellular vesicles, with equal efficacy to intact stem cells, is highly desirable for future therapeutic purposes. This chapter will discuss current research into the biological activity and therapeutic application of extracellular vesicles derived from mesenchymal stem cells. With a focus on approaches for the large-scale production and isolation of extracellular vesicles will enable the transition of extracellular vesicle research into clinical application.
Abbreviations
- ADSC:
-
Adipose-derived mesenchymal stem cells
- AMI:
-
Acute myocardial infarction
- BM-MSC:
-
Bone marrow-derived mesenchymal stem cells
- CIMVs:
-
Cytochalasin B-induced microvesicles
- CKD:
-
Chronic kidney disease
- DC:
-
Dendritic cells
- dsDNA:
-
Double-stranded DNA
- EVs:
-
Extracellular vesicles
- GvHD:
-
Graft-versus-host disease
- ICG:
-
Indocyanine green
- ISEV:
-
The International Society for Extracellular Vesicles
- LPS:
-
Lipopolysaccharide
- MHC:
-
Major histocompatibility complex
- miRNA:
-
MicroRNA
- MISEV:
-
Minimal information for studies of extracellular vesicles
- mRNA:
-
Messenger RNA
- MSC:
-
Mesenchymal stem cells
- mtDNA:
-
Mitochondrial DNA
- MVB:
-
Multivesicular body
- MVs:
-
Microvesicles
- PBMCs:
-
Peripheral blood mononuclear cells
- PHA:
-
Phytohemagglutinin
- SC:
-
Stem cells
- ssDNA:
-
Single-stranded DNA
- TNTs:
-
Tunneling nanotubes
- UACR:
-
Urinary albumin creatinine ratio
- UC-MSC:
-
Umbilical cord mesenchymal stem cells
- WJ-MSC:
-
Wharton’s jelly-derived mesenchymal stem cells
References
Al-Dossary AA, Strehler EE, Martin-Deleon PA (2013) Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm. PLoS One 8:e80181
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345
Benz EW Jr, Moses HL (1974) Small, virus-like particles detected in bovine sera by electron microscopy. J Natl Cancer Inst 52:1931–1934
Blazquez R, Sanchez-Margallo FM, de la Rosa O, Dalemans W, Alvarez V, Tarazona R, Casado JG (2014) Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol 5:556
Boukelmoune N, Chiu GS, Kavelaars A, Heijnen CJ (2018) Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin. Acta Neuropathol Commun 6:139
Bruno S, Tapparo M, Collino F, Chiabotto G, Deregibus MC, Soares Lindoso R, Neri F, Kholia S (2017) Renal regenerative potential of different extracellular vesicle populations derived from bone marrow mesenchymal stromal cells. Tissue Eng Part A 23:1262–1273
Budoni M, Fierabracci A, Luciano R, Petrini S, Di Ciommo V, Muraca M (2013) The immunosuppressive effect of mesenchymal stromal cells on B lymphocytes is mediated by membrane vesicles. Cell Transplant 22:369–379
Burt R, Dey A, Aref S, Aguiar M, Akarca A, Bailey K, Day W, Hooper S (2019) Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress. Blood 134:1415–1429
Chen J, Ren S, Duscher D, Kang Y, Liu Y, Wang C, Yuan M, Guo G (2019) Exosomes from human adipose-derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function. J Cell Physiol 234:23097–23110
Cho BS, Kim JO, Ha DH, Yi YW (2018) Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther 9:187
Colombo M, Raposo G, Thery C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289
Cosenza S, Toupet K, Maumus M, Luz-Crawford P, Blanc-Brude O, Jorgensen C, Noel D (2018) Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics 8:1399–1410
Court FA, Hendriks WT, MacGillavry HD, Alvarez J, van Minnen J (2008) Schwann cell to axon transfer of ribosomes: toward a novel understanding of the role of glia in the nervous system. J Neurosci 28:11024–11029
Del Fattore A, Luciano R, Pascucci L, Goffredo BM, Giorda E, Scapaticci M, Fierabracci A, Muraca M (2015) Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes. Cell Transplant 24:2615–2627
Del Piccolo N, Placone J, He L, Agudelo SC, Hristova K (2012) Production of plasma membrane vesicles with chloride salts and their utility as a cell membrane mimetic for biophysical characterization of membrane protein interactions. Anal Chem 84:8650–8655
Deng S, Zhou X, Ge Z, Song Y, Wang H, Liu X, Zhang D (2019) Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization. Int J Biochem Cell Biol 114:105564
Di Trapani M, Bassi G, Midolo M, Gatti A, Kamga PT, Cassaro A, Carusone R, Adamo A (2016) Differential and transferable modulatory effects of mesenchymal stromal cell-derived extracellular vesicles on T, B and NK cell functions. Sci Rep 6:24120
Ding J, Wang X, Chen B, Zhang J, Xu J (2019) Exosomes derived from human bone marrow mesenchymal stem cells stimulated by deferoxamine accelerate cutaneous wound healing by promoting angiogenesis. Biomed Res Int 2019:9742765
Drommelschmidt K, Serdar M, Bendix I, Herz J, Bertling F, Prager S, Keller M, Ludwig AK (2017) Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav Immun 60:220–232
Durrani S, Ashraf M, Jiang S, Haider KH (2010) Hypoxia inducible factor-1α dependent miR-210 is a critical regulator of paracrine activity in preconditioned mesenchymal stem cells for angiogenic growth factor expression. Circulation Suppl.122:A17923
Efimenko AY, Kochegura TN, Akopyan ZA, Parfyonova YV (2015) Autologous stem cell therapy: how aging and chronic diseases affect stem and progenitor cells. Biores Open Access 4:26–38
Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, Takikawa T, Yoshida T (2019) Cardiomyocytes capture stem cell-derived, anti-apoptotic microRNA-214 via clathrin-mediated endocytosis in acute myocardial infarction. J Biol Chem 294:11665–11674
Elmadbouh I, Haider KH, Shujia J, Niagara MI, Gang L, Ashraf M (2007) Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J Mol Cell Cardiol 42:792–803
Eyer K, Herger M, Kramer SD, Dittrich PS (2014) Cell-free microfluidic determination of P-glycoprotein interactions with substrates and inhibitors. Pharm Res 31:3415–3425
Falchi AM, Sogos V, Saba F, Piras M, Congiu T, Piludu M (2013) Astrocytes shed large membrane vesicles that contain mitochondria, lipid droplets and ATP. Histochem Cell Biol 139:221–231
Fang S, Xu C, Zhang Y, Xue C, Yang C, Bi H, Qian X, Wu M (2016) Umbilical cord-derived mesenchymal stem cell-derived exosomal microRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-beta/SMAD2 pathway during wound healing. Stem Cells Transl Med 5:1425–1439
Feng Y, Zhu R, Shen J, Wu J, Lu W, Zhang J, Zhang J, Liu K (2019) Human bone marrow mesenchymal stem cells rescue endothelial cells experiencing chemotherapy stress by mitochondrial transfer via tunneling nanotubes. Stem Cells Dev 28:674–682
Fujii S, Miura Y, Fujishiro A, Shindo T, Shimazu Y, Hirai H, Tahara H, Takaori-Kondo A (2018) Graft-versus-host disease amelioration by human bone marrow mesenchymal stromal/stem cell-derived extracellular vesicles is associated with peripheral preservation of naive T cell populations. Stem Cells 36:434–445
Galieva LR, James V, Mukhamedshina YO, Rizvanov AA (2019) Therapeutic potential of extracellular vesicles for the treatment of nerve disorders. Front Neurosci 13:163
Gomzikova MO, Rizvanov AA (2017) Current trends in regenerative medicine: from cell to cell-free therapy. Bionanoscience 7:240–245
Gomzikova MO, Zhuravleva MN, Miftakhova RR, Arkhipova SS, Evtugin VG, Khaiboullina SF, Kiyasov AP, Persson JL (2017) Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental cells. Oncotarget 8:70496–70507
Gomzikova M, Kletukhina S, Kurbangaleeva S, Rizvanov A (2018) Evaluation of cytochalasin B-induced membrane vesicles fusion specificity with target cells. Biomed Res Int 2018:7053623
Gomzikova MO, James V, Rizvanov AA (2019a) Therapeutic application of mesenchymal stem cells derived extracellular vesicles for immunomodulation. Front Immunol 10:2663
Gomzikova MO, Zhuravleva MN, Vorobev VV, Salafutdinov II, Laikov AV, Kletukhina SK, Martynova EV, Tazetdinova LG (2019b) Angiogenic activity of cytochalasin B-induced mem-brane vesicles of human mesenchymal stem cells. Cell 9(1):95. https://doi.org/10.3390/cells9010095
Gomzikova MO, Aimaletdinov AM, Bondar OV, Starostina IG, Gorshkova NV, Neustroeva OA, Kletukhina SK, Kurbangaleeva SV (2020a) Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells. Sci Rep 10:10740
Gomzikova MO, Kletukhina SK, Kurbangaleeva SV, Neustroeva OA, Vasileva OS, Garanina EE, Khaiboullina SF, Rizvanov AA (2020b) Mesenchymal stem cell derived biocompatible membrane vesicles demonstrate immunomodulatory activity inhibiting activation and proliferation of human mononuclear cells. Pharmaceutics 12(6):577. https://doi.org/10.3390/pharmaceutics12060577
Gomzikova MO, James V, Rizvanov AA (2021) Mitochondria donation by mesenchymal stem cells: current understanding and mitochondria transplantation strategies. Front Cell Dev Biol 9:653322
Grange C, Tritta S, Tapparo M, Cedrino M, Tetta C, Camussi G, Brizzi MF (2019) Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci Rep 9:4468
Griffiths GS, Galileo DS, Reese K, Martin-Deleon PA (2008) Investigating the role of murine epididymosomes and uterosomes in GPI-linked protein transfer to sperm using SPAM1 as a model. Mol Reprod Dev 75:1627–1636
Groot M, Lee H (2020) Sorting mechanisms for MicroRNAs into extracellular vesicles and their associated diseases. Cell 9(4):1044. https://doi.org/10.3390/cells9041044
Gyorgy B, Szabo TG, Turiak L, Wright M, Herczeg P, Ledeczi Z, Kittel A, Polgar A (2012) Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle) signatures in joint diseases. PLoS One 7:e49726
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
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: Article 23, 1–12
Haider KH, Ashraf M (2005) Bone marrow stem cell transplantation for cardiac repair. Am J Physiol Heart Circ Physiol 288:2557–2567
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
Haider KH, Aziz S (2017) Paracrine hypothesis and cardiac repair. Int J Stem Cell Res Transplant 5(1):265–267
Haider KH, Jiang S, Niagara MI, 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. Circ Res 103:1300–1308
Han LCY, Niu J, Peng L, Mao Z, Gaoa C (2016) Encapsulation of a photosensitizer into cell membrane capsules for photodynamic therapy. RSC Adv 6, 37212–37220
Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535:551–555
Hough KP, Trevor JL, Strenkowski JG, Wang Y, Chacko BK, Tousif S, Chanda D, Steele C (2018) Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells. Redox Biol 18:54–64
Hu B, Chen S, Zou M, He Z, Shao S, Liu B (2016) Effect of extracellular vesicles on neural functional recovery and immunologic suppression after rat cerebral apoplexy. Cell Physiol Biochem 40:155–162
Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, Rowlands DJ, Quadri SK (2012) Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med 18:759–765
Jiang D, Xiong G, Feng H, Zhang Z, Chen P, Yan B, Chen L, Gandhervin K (2019) Donation of mitochondria by iPSC-derived mesenchymal stem cells protects retinal ganglion cells against mitochondrial complex I defect-induced degeneration. Theranostics 9:2395–2410
Jiang D, Chen FX, Zhou H, Lu YY, Tan H, Yu SJ, Yuan J, Liu H (2020) Bioenergetic crosstalk between mesenchymal stem cells and various ocular cells through the intercellular trafficking of mitochondria. Theranostics 10:7260–7272
Kang J, Li Z, Zhi Z, Wang S, Xu G (2019) MiR-21 derived from the exosomes of MSCs regulates the death and differentiation of neurons in patients with spinal cord injury. Gene Ther 26:491–503
Keller S, Rupp C, Stoeck A, Runz S, Fogel M, Lugert S, Hager HD, Abdel-Bakky MS (2007) CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int 72:1095–1102
Khare D, Or R, Resnick I, Barkatz C, Almogi-Hazan O, Avni B (2018) Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes. Front Immunol 9:3053
Khatri M, Richardson LA, Meulia T (2018) Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res Ther 9:17
Koch M, Lemke A, Lange C (2015) Extracellular vesicles from MSC modulate the immune response to renal allografts in a MHC disparate rat model. Stem Cells Int 2015:486141
Kordelas L, Rebmann V, Ludwig AK, Radtke S, Ruesing J, Doeppner TR, Epple M, Horn PA (2014) MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia 28:970–973
Laso-Garcia F, Ramos-Cejudo J, Carrillo-Salinas FJ, Otero-Ortega L, Feliu A, Gomez-de Frutos M, Mecha M, Diez-Tejedor E (2018) Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis. PLoS One 13:e0202590
Lasser C, Alikhani VS, Ekstrom K, Eldh M, Paredes PT, Bossios A, Sjostrand M, Gabrielsson S (2011) Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med 9:9
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
Levanen B, Bhakta NR, Torregrosa Paredes P, Barbeau R, Hiltbrunner S, Pollack JL, Skold CM, Svartengren M (2013) Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients. J Allergy Clin Immunol 131:894–903
Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y (2013) Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 22:845–854
Li H, Wang C, He T, Zhao T, Chen YY, Shen YL, Zhang X, Wang LL (2019) Mitochondrial transfer from bone marrow mesenchymal stem cells to motor neurons in spinal cord injury rats via gap junction. Theranostics 9:2017–2035
Lim JH, Park J, Oh EH, Ko HJ, Hong S, Park TH (2014) Nanovesicle-based bioelectronic nose for the diagnosis of lung cancer from human blood. Adv Healthc Mater 3:360–366
Lin TK, Chen SD, Chuang YC, Lan MY, Chuang JH, Wang PW, Hsu TY, Wang FS (2019) Mitochondrial transfer of Wharton’s jelly mesenchymal stem cells eliminates mutation burden and rescues mitochondrial bioenergetics in rotenone-stressed MELAS fibroblasts. Oxidative Med Cell Longev 2019:9537504
Liu K, Guo L, Zhou Z, Pan M, Yan C (2019) Mesenchymal stem cells transfer mitochondria into cerebral microvasculature and promote recovery from ischemic stroke. Microvasc Res 123:74–80
Luz-Crawford P, Hernandez J, Djouad F, Luque-Campos N, Caicedo A, Carrere-Kremer S, Brondello JM, Vignais ML (2019) Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer. Stem Cell Res Ther 10:232
Machtinger R, Laurent LC, Baccarelli AA (2016) Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update 22:182–193
Mao Z, Cartier R, Hohl A, Farinacci M, Dorhoi A, Nguyen TL, Mulvaney P, Ralston J (2011) Cells as factories for humanized encapsulation. Nano Lett 11:2152–2156
Momen-Heravi F, Balaj L, Alian S, Mantel PY, Halleck AE, Trachtenberg AJ, Soria CE, Oquin S (2013) Current methods for the isolation of extracellular vesicles. Biol Chem 394:1253–1262
Morrison TJ, Jackson MV, Cunningham EK, Kissenpfennig A, McAuley DF, O’Kane CM, Krasnodembskaya AD (2017) Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med 196:1275–1286
Nassar W, El-Ansary M, Sabry D, Mostafa MA, Fayad T, Kotb E, Temraz M, Saad AN (2016) Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res 20:21
Newell C, Sabouny R, Hittel DS, Shutt TE, Khan A, Klein MS, Shearer J (2018) Mesenchymal stem cells shift mitochondrial dynamics and enhance oxidative phosphorylation in recipient cells. Front Physiol 9:1572
Ni J, Liu X, Yin Y, Zhang P, Xu YW, Liu Z (2019) Exosomes derived from TIMP2-modified human umbilical cord mesenchymal stem cells enhance the repair effect in rat model with myocardial infarction possibly by the Akt/Sfrp2 pathway. Oxidative Med Cell Longev 2019:1958941
Oshchepkova A, Neumestova A, Matveeva V, Artemyeva L, Morozova K, Kiseleva E, Zenkova M et al (2019) Cytochalasin-B-inducible nanovesicle mimics of natural extracellular vesicles that are capable of nucleic acid transfer. Micromachines (Basel) 10(11):750. https://doi.org/10.3390/mi10110750
Otero-Ortega L, Laso-Garcia F, Frutos MCG, Diekhorst L, Martinez-Arroyo A, Alonso-Lopez E, Garcia-Bermejo ML et al (2020) Low dose of extracellular vesicles identified that promote recovery after ischemic stroke. Stem Cell Res Ther 11:70
Otsuru S, Desbourdes L, Guess AJ, Hofmann TJ, Relation T, Kaito T, Dominici M et al (2018) Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy 20:62–73
Palanisamy V, Sharma S, Deshpande A, Zhou H, Gimzewski J, Wong DT (2010) Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS One 5:e8577
Peng LH, Zhang YH, Han LJ, Zhang CZ, Wu JH, Wang XR, Gao JQ, Mao ZW (2015) Cell Membrane Capsules for Encapsulation of Chemotherapeutic and Cancer Cell Targeting in Vivo. ACS Appl Mater Interfaces 7(33):18628–37. https://doi.org/10.1021/acsami.5b05065. Epub 2015 Aug 17
Peruzzotti-Jametti L, Bernstock JD, Manferrari G, Rogall R, Fernandez-Vizarra E, Williamson JC, Braga A et al (2020) Neural stem cells traffic functional mitochondria via extracellular vesicles to correct mitochondrial dysfunction in target cells. bioRxiv 2020.01.29.923441
Phinney DG, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix CM, Stolz DB et al (2015) Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun 6:8472
Piccin A, Murphy WG, Smith OP (2007) Circulating microparticles: pathophysiology and clinical implications. Blood Rev 21:157–171
Pick H, Schmid EL, Tairi AP, Ilegems E, Hovius R, Vogel H (2005) Investigating cellular signaling reactions in single attoliter vesicles. J Am Chem Soc 127:2908–2912
Pisitkun T, Shen RF, Knepper MA (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A 101:13368–13373
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172
Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–856
Ren S, Chen J, Duscher D, Liu Y, Guo G, Kang Y, Xiong H, Zhan P (2019) Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways. Stem Cell Res Ther 10:47
Riazifar M, Mohammadi MR, Pone EJ, Yeri A, Lasser C, Segaliny AI, McIntyre LL, Shelke GV (2019) Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano 13:6670–6688
Ruppert KA, Nguyen TT, Prabhakara KS, Toledano Furman NE, Srivastava AK, Harting MT et al (2018) Human mesenchymal stromal cell-derived extracellular vesicles modify microglial response and improve clinical outcomes in experimental spinal cord injury. Sci Rep 8:480
Ryan JM, Barry FP, Murphy JM, Mahon BP (2005) Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (Lond) 2:8
Sengupta V, Sengupta S, Lazo A, Woods P, Nolan A, Bremer N (2020) Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem Cells Dev 29:747–754
Seo Y, Kim HS, Hong IS (2019) Stem cell-derived extracellular vesicles as immunomodulatory therapeutics. Stem Cells Int 2019:5126156
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
Shen B, Liu J, Zhang F, Wang Y, Qin Y, Zhou Z, Qiu J, Fan Y (2016) CCR2 positive exosome released by mesenchymal stem cells suppresses macrophage functions and alleviates ischemia/reperfusion-induced renal injury. Stem Cells Int 2016:1240301
Sheng G, Chen Y, Han L, Huang Y, Liu X, Li L, Mao Z (2016) Encapsulation of indocyanine green into cell membrane capsules for photothermal cancer therapy. Acta Biomater 43:251–261
Shigemoto-Kuroda T, Oh JY, Kim DK, Jeong HJ, Park SY, Lee HJ, Park JW et al (2017) MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: type 1 diabetes and uveoretinitis. Stem Cell Reports 8:1214–1225
Skotland T, Sagini K, Sandvig K, Llorente A (2020) An emerging focus on lipids in extracellular vesicles. Adv Drug Deliv Rev 159:308–321
Song JY, Kang HJ, Hong JS, Kim CJ, Shim JY, Lee CW, Choi J (2017) Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages. Sci Rep 7:9412
Spinosa M, Lu G, Su G, Bontha SV, Gehrau R, Salmon MD, Smith JR, Weiss ML, Mas VR, Upchurch GR Jr, Sharma AK (2018) Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147. FASEB J. 32(11):fj201701138RR. https://doi.org/10.1096/fj.201701138RR. Epub ahead of print
Street JM, Barran PE, Mackay CL, Weidt S, Balmforth C, Walsh TS, Chalmers RT et al (2012) Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med 10:5
Sun XH, Wang X, Zhang Y, Hui J (2019) Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway. Thromb Res 177:23–32
Syromiatnikova KI, Masgutova G, Gomzikova M, Kabwe E, Bek J, Andreeva D, Masgutov R, Mullakhmetova A, James V, Rizvanov A (2020) Analyzing the effectiveness of adipose tissue stem cell and microvesicle therapy in premature skin aging caused by chronic exposure to ultraviolet radiation. BioNanoScience 10:991–997
Teng XM, Chen L, Chen WQ, Yang JJ, Yang ZY, Shen ZY (2015) Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell Physiol Biochem 37:2415–2424
Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7:1535750
Thomi G, Surbek D, Haesler V, Joerger-Messerli M, Schoeberlein A (2019) Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res Ther 10:105
Tseng N, Lambie SC, Huynh CQ, Sanford B, Patel M, Herson PS, Ormond DR (2021) Mitochondrial transfer from mesenchymal stem cells improves neuronal metabolism after oxidant injury in vitro: The role of Miro1. J Cereb Blood Flow Metab. 41(4):761–770. https://doi.org/10.1177/0271678X20928147. Epub 2020 Jun 5
Usmani S, Sivagnanalingam U, Tkachenko O, Nunez L, Shand JC, Mullen CA (2019) Support of acute lymphoblastic leukemia cells by nonmalignant bone marrow stromal cells. Oncol Lett 17:5039–5049
van den Akker F, Vrijsen KR, Deddens JC, Buikema JW, Mokry M, van Laake LW, Doevendans PA, Sluijter JPG (2018) Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles. Heliyon 4(6):e00642. https://doi.org/10.1016/j.heliyon.2018.e00642
Wan Y, Wang L, Zhu C, Zheng Q, Wang G, Tong J, Fang Y, Xia Y (2018) Aptamer-conjugated extracellular nanovesicles for targeted drug delivery. Cancer Res 78:798–808
Wang L, Gu Z, Zhao X, Yang N, Wang F, Deng A, Zhao S, Luo L (2016) Extracellular vesicles released from human umbilical cord-derived mesenchymal stromal cells prevent life-threatening acute graft-versus-host disease in a mouse model of allogeneic hematopoietic stem cell transplantation. Stem Cells Dev 25:1874–1883
Wang J, Liu X, Qiu Y, Shi Y, Cai J, Wang B, Wei X, Ke Q (2018) Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell-induced chemoresistance on T cell acute lymphoblastic leukemia cells. J Hematol Oncol 11:11
Wen D, Peng Y, Liu D, Weizmann Y, Mahato RI (2016) Mesenchymal stem cell and derived exosome as small RNA carrier and immunomodulator to improve islet transplantation. J Control Release 238:166–175
Willis GR, Fernandez-Gonzalez A, Anastas J, Vitali SH, Liu X, Ericsson M, Kwong A, Mitsialis SA (2018) Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation. Am J Respir Crit Care Med 197:104–116
Willms E, Johansson HJ, Mager I, Lee Y, Blomberg KE, Sadik M, Alaarg A, Smith CI (2016) Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep 6:22519
Witek RP, Yang L, Liu R, Jung Y, Omenetti A, Syn WK, Choi SS, Cheong Y (2009) Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells. Gastroenterology 136: 320–330 e2
Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288
Wu HW, Oliver AE, Ngassam VN, Yee CK, Parikh AN, Yeh Y (2012) Preparation, characterization, and surface immobilization of native vesicles obtained by mechanical extrusion of mammalian cells. Integr Biol 4:685–692
Xu LQ. Lin MJ, Li YP, Li S, Chen SJ, Wei CJ (2017) Preparation of Plasma Membrane Vesicles from Bone Marrow Mesenchymal Stem Cells for Potential Cytoplasm Replacement Therapy. J Vis Exp (123), e55741. https://doi.org/10.3791/55741
Yamamoto T, Kosaka N, Ochiya T (2019) Latest advances in extracellular vesicles: from bench to bedside. Sci Technol Adv Mater 20:746–757
Yang Y, Ye G, Zhang YL, He HW, Yu BQ, Hong YM, You W, Li X (2020) Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells. Neural Regen Res 15:464–472
Yi X, Wei X, Lv H, An Y, Li L, Lu P, Yang Y, Zhang Q (2019) Exosomes derived from microRNA-30b-3p-overexpressing mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting SAA3. Exp Cell Res 383:111454
Yin K, Wang S, Zhao RC (2019) Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomark Res 7:8
Yu B, Zhang X, Li X (2014) Exosomes derived from mesenchymal stem cells. Int J Mol Sci 15:4142–4157
Zhang B, Yin Y, Lai RC, Tan SS, Choo AB, Lim SK (2014) Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev 23:1233–1244
Zhang B, Wu X, Zhang X, Sun Y, Yan Y, Shi H, Zhu Y, Wu L (2015) Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/beta-catenin pathway. Stem Cells Transl Med 4:513–522
Zhang Y, Chopp M, Zhang ZG, Katakowski M, Xin H, Qu C, Ali M et al (2017) Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem Int 111:69–81
Zhang J, Zhang J, Zhao L, Xin Y, Liu S, Cui W (2019) Differential roles of microtubules in the two formation stages of membrane nanotubes between human mesenchymal stem cells and neonatal mouse cardiomyocytes. Biochem Biophys Res Commun 512:441–447
Zhang B, Tian X, Hao J, Xu G, Zhang W (2020a) Mesenchymal stem cell-derived extracellular vesicles in tissue regeneration. Cell Transplant 29:963689720908500
Zhang S, Jiang L, Hu H, Wang H, Wang X, Jiang J, Ma Y et al (2020b) Pretreatment of exosomes derived from hUCMSCs with TNF-alpha ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage. Life Sci 246:117401
Zhang X, Hubal MJ, Kraus VB (2020c) Immune cell extracellular vesicles and their mitochondrial content decline with ageing. Immun Ageing 17:1
Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes 67:235–247
Zhao J, Li X, Hu J, Chen F, Qiao S, Sun X, Gao L, Xie J (2019) Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization. Cardiovasc Res 115:1205–1216
Zhou Y, Xu H, Xu W, Wang B, Wu H, Tao Y, Zhang B et al (2013) Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther 4:34
Zou X, Gu D, Xing X, Cheng Z, Gong D, Zhang G, Zhu Y (2016) Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats. Am J Transl Res 8:4289–4299
Zou X, Kwon SH, Jiang K, Ferguson CM, Puranik AS, Zhu X, Lerman LO (2018) Renal scattered tubular-like cells confer protective effects in the stenotic murine kidney mediated by release of extracellular vesicles. Sci Rep 8:1263
Acknowledgments
This paper has been supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030). This work was funded by RSF according to the research project â„–21-75-10035.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2022 Springer Nature Singapore Pte Ltd.
About this entry
Cite this entry
Gomzikova, M.O., James, V., Rizvanov, A.A. (2022). Extracellular Vesicles Derived from Mesenchymal Stem Cells. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_48-1
Download citation
DOI: https://doi.org/10.1007/978-981-16-6016-0_48-1
Received:
Accepted:
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-6016-0
Online ISBN: 978-981-16-6016-0
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences