Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine?
Abstract
:1. Introduction
2. Stem Cells
3. Stem Cells and Regenerative Medicine
4. Stem Cells Drawbacks in Regenerative Medicine
5. Extracellular Vesicles (EVs)
6. Extracellular Vesicles Composition
7. Extracellular Vesicles-Based Regenerative Medicine
8. Induced Pluripotent Stem Cell Derived EVs in Regenerative Medicine
9. EVs as a Cargo Delivery System
10. EVs Functionalized Scaffolds in Regenerative Medicine
11. Vantages and Disadvantages in the Use of Stem Cell-EV Based Therapies
12. Conclusions and Future Perspective in EV-Based Therapies in Regenerative Medicine
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Guild, W.R.; Harrison, J.H.; Merrill, J.P.; Murray, J. Successful homotransplantation of the kidney in an identical twin. Trans. Am. Clin. Climatol. Assoc. 1955, 67, 167–173. [Google Scholar] [PubMed]
- Gatti, R.A.; Meuwissen, H.J.; Allen, H.D.; Hong, R.; Good, R.A. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 1968, 2, 1366–1369. [Google Scholar] [CrossRef]
- Weissman, I.L. Translating stem and progenitor cell biology to the clinic: Barriers and opportunities. Science 2000, 287, 1442–1446. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Menasche, P.; Vanneaux, V.; Hagege, A.; Bel, A.; Cholley, B.; Cacciapuoti, I.; Parouchev, A.; Benhamouda, N.; Tachdjian, G.; Tosca, L.; et al. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: First clinical case report. Eur. Heart J. 2015, 36, 2011–2017. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwartz, S.D.; Regillo, C.D.; Lam, B.L.; Eliott, D.; Rosenfeld, P.J.; Gregori, N.Z.; Hubschman, J.P.; Davis, J.L.; Heilwell, G.; Spirn, M.; et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: Follow-up of two open-label phase 1/2 studies. Lancet 2015, 385, 509–516. [Google Scholar] [CrossRef]
- Rossant, J. Stem cells from the Mammalian blastocyst. Stem Cells 2001, 19, 477–482. [Google Scholar] [CrossRef]
- Jaenisch, R.; Young, R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 2008, 132, 567–582. [Google Scholar] [CrossRef] [Green Version]
- De Miguel, M.P.; Fuentes-Julian, S.; Alcaina, Y. Pluripotent stem cells: Origin, maintenance and induction. Stem Cell Rev. Rep. 2010, 6, 633–649. [Google Scholar] [CrossRef]
- Ratajczak, M.Z.; Zuba-Surma, E.; Kucia, M.; Poniewierska, A.; Suszynska, M.; Ratajczak, J. Pluripotent and multipotent stem cells in adult tissues. Adv. Med. Sci. 2012, 57, 1–17. [Google Scholar] [CrossRef]
- Bentzinger, C.F.; Wang, Y.X.; von Maltzahn, J.; Rudnicki, M.A. The emerging biology of muscle stem cells: Implications for cell-based therapies. BioEssays News Rev. Mol. Cell. Dev. Biol. 2013, 35, 231–241. [Google Scholar] [CrossRef] [Green Version]
- Beck, B.; Blanpain, C. Mechanisms regulating epidermal stem cells. EMBO J. 2012, 31, 2067–2075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ilic, D.; Polak, J.M. Stem cells in regenerative medicine: Introduction. Br. Med. Bull. 2011, 98, 117–126. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bongso, A.; Richards, M. History and perspective of stem cell research. Best Pract. Res. Clin. Obstet. Gynaecol. 2004, 18, 827–842. [Google Scholar] [CrossRef] [PubMed]
- Rossant, J. Stem cells and early lineage development. Cell 2008, 132, 527–531. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131, 861–872. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Lazaro, I.; Yilmazer, A.; Kostarelos, K. Induced pluripotent stem (iPS) cells: A new source for cell-based therapeutics? J. Control. Release Off. J. Control. Release Soc. 2014, 185, 37–44. [Google Scholar] [CrossRef]
- Yu, B.; Zhang, X.; Li, X. Exosomes derived from mesenchymal stem cells. Int. J. Mol. Sci. 2014, 15, 4142–4157. [Google Scholar] [CrossRef] [Green Version]
- Omole, A.E.; Fakoya, A.O.J. Ten years of progress and promise of induced pluripotent stem cells: Historical origins, characteristics, mechanisms, limitations, and potential applications. PeerJ 2018, 6, e4370. [Google Scholar] [CrossRef] [Green Version]
- Malik, N.; Rao, M.S. A review of the methods for human iPSC derivation. Methods Mol. Biol. 2013, 997, 23–33. [Google Scholar]
- Mohammadian, M.; Shamsasenjan, K.; Lotfi Nezhad, P.; Talebi, M.; Jahedi, M.; Nickkhah, H.; Minayi, N.; Movassagh Pour, A. Mesenchymal stem cells: New aspect in cell-based regenerative therapy. Adv. Pharm. Bull. 2013, 3, 433–437. [Google Scholar]
- Gallico, G.G., 3rd; O’Connor, N.E.; Compton, C.C.; Kehinde, O.; Green, H. Permanent coverage of large burn wounds with autologous cultured human epithelium. N. Engl. J. Med. 1984, 311, 448–451. [Google Scholar] [CrossRef] [PubMed]
- Thivolet, J.; Faure, M.; Demidem, A.; Mauduit, G. Long-term survival and immunological tolerance of human epidermal allografts produced in culture. Transplantation 1986, 42, 274–280. [Google Scholar] [CrossRef] [PubMed]
- Rheinwald, J.G.; Green, H. Serial cultivation of strains of human epidermal keratinocytes: The formation of keratinizing colonies from single cells. Cell 1975, 6, 331–343. [Google Scholar] [CrossRef]
- Ronfard, V.; Rives, J.M.; Neveux, Y.; Carsin, H.; Barrandon, Y. Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix. Transplantation 2000, 70, 1588–1598. [Google Scholar] [CrossRef]
- Hirsch, T.; Rothoeft, T.; Teig, N.; Bauer, J.W.; Pellegrini, G.; De Rosa, L.; Scaglione, D.; Reichelt, J.; Klausegger, A.; Kneisz, D.; et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature 2017, 551, 327–332. [Google Scholar] [CrossRef]
- Kroon, E.; Martinson, L.A.; Kadoya, K.; Bang, A.G.; Kelly, O.G.; Eliazer, S.; Young, H.; Richardson, M.; Smart, N.G.; Cunningham, J.; et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol. 2008, 26, 443–452. [Google Scholar] [CrossRef]
- Trivedi, H.L.; Vanikar, A.V.; Thakker, U.; Firoze, A.; Dave, S.D.; Patel, C.N.; Patel, J.V.; Bhargava, A.B.; Shankar, V. Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin. Transplant. Proc. 2008, 40, 1135–1139. [Google Scholar] [CrossRef]
- Menasche, P.; Alfieri, O.; Janssens, S.; McKenna, W.; Reichenspurner, H.; Trinquart, L.; Vilquin, J.T.; Marolleau, J.P.; Seymour, B.; Larghero, J.; et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: First randomized placebo-controlled study of myoblast transplantation. Circulation 2008, 117, 1189–1200. [Google Scholar] [CrossRef] [Green Version]
- Hagege, A.A.; Marolleau, J.P.; Vilquin, J.T.; Alheritiere, A.; Peyrard, S.; Duboc, D.; Abergel, E.; Messas, E.; Mousseaux, E.; Schwartz, K.; et al. Skeletal myoblast transplantation in ischemic heart failure: Long-term follow-up of the first phase I cohort of patients. Circulation 2006, 114, I108–I113. [Google Scholar] [CrossRef] [Green Version]
- Burt, R.K.; Loh, Y.; Cohen, B.; Stefoski, D.; Balabanov, R.; Katsamakis, G.; Oyama, Y.; Russell, E.J.; Stern, J.; Muraro, P.; et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: A phase I/II study. Lancet Neurol. 2009, 8, 244–253. [Google Scholar] [CrossRef]
- Bjorklund, L.M.; Sanchez-Pernaute, R.; Chung, S.; Andersson, T.; Chen, I.Y.; McNaught, K.S.; Brownell, A.L.; Jenkins, B.G.; Wahlestedt, C.; Kim, K.S.; et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl. Acad. Sci. USA 2002, 99, 2344–2349. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lindvall, O.; Kokaia, Z. Stem cells for the treatment of neurological disorders. Nature 2006, 441, 1094–1096. [Google Scholar] [CrossRef] [PubMed]
- Nasef, A.; Ashammakhi, N.; Fouillard, L. Immunomodulatory effect of mesenchymal stromal cells: Possible mechanisms. Regen. Med. 2008, 3, 531–546. [Google Scholar] [CrossRef] [PubMed]
- Williams, A.R.; Hare, J.M. Mesenchymal stem cells: Biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ. Res. 2011, 109, 923–940. [Google Scholar] [CrossRef] [Green Version]
- Bernardo, M.E.; Fibbe, W.E. Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell 2013, 13, 392–402. [Google Scholar] [CrossRef] [Green Version]
- Yin, Y.; Li, X.; He, X.T.; Wu, R.X.; Sun, H.H.; Chen, F.M. Leveraging Stem Cell Homing for Therapeutic Regeneration. J. Dent. Res. 2017, 96, 601–609. [Google Scholar] [CrossRef]
- Caplan, A.I.; Correa, D. The MSC: An injury drugstore. Cell Stem Cell 2011, 9, 11–15. [Google Scholar] [CrossRef] [Green Version]
- Han, Y.; Li, X.; Zhang, Y.; Han, Y.; Chang, F.; Ding, J. Mesenchymal Stem Cells for Regenerative Medicine. Cells 2019, 8, 886. [Google Scholar] [CrossRef] [Green Version]
- Kern, S.; Eichler, H.; Stoeve, J.; Kluter, H.; Bieback, K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006, 24, 1294–1301. [Google Scholar] [CrossRef]
- Pittenger, M.F.; Mackay, A.M.; Beck, S.C.; Jaiswal, R.K.; Douglas, R.; Mosca, J.D.; Moorman, M.A.; Simonetti, D.W.; Craig, S.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284, 143–147. [Google Scholar] [CrossRef] [Green Version]
- Hass, R.; Kasper, C.; Bohm, S.; Jacobs, R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun. Signal. CCS 2011, 9, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marquez-Curtis, L.A.; Janowska-Wieczorek, A.; McGann, L.E.; Elliott, J.A. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects. Cryobiology 2015, 71, 181–197. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, X.; Yang, M.; Lin, L.; Chen, P.; Ma, K.T.; Zhou, C.Y.; Ao, Y.F. Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose--derived stem cells in vitro and in vivo. Calcif. Tissue Int. 2006, 79, 169–178. [Google Scholar] [CrossRef] [PubMed]
- Hou, T.; Xu, J.; Wu, X.; Xie, Z.; Luo, F.; Zhang, Z.; Zeng, L. Umbilical cord Wharton’s Jelly: A new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Eng. A 2009, 15, 2325–2334. [Google Scholar] [CrossRef]
- Huang, G.T.; Gronthos, S.; Shi, S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: Their biology and role in regenerative medicine. J. Dent. Res. 2009, 88, 792–806. [Google Scholar] [CrossRef]
- Ullah, I.; Subbarao, R.B.; Rho, G.J. Human mesenchymal stem cells-current trends and future prospective. Biosci. Rep. 2015, 35, e00191. [Google Scholar] [CrossRef]
- Gimble, J.M.; Katz, A.J.; Bunnell, B.A. Adipose-derived stem cells for regenerative medicine. Circ. Res. 2007, 100, 1249–1260. [Google Scholar] [CrossRef]
- Zuk, P.A.; Zhu, M.; Mizuno, H.; Huang, J.; Futrell, J.W.; Katz, A.J.; Benhaim, P.; Lorenz, H.P.; Hedrick, M.H. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng. 2001, 7, 211–228. [Google Scholar] [CrossRef] [Green Version]
- Mazini, L.; Rochette, L.; Amine, M.; Malka, G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int. J. Mol. Sci. 2019, 20, 2523. [Google Scholar] [CrossRef] [Green Version]
- Mizuno, H. Adipose-derived stem and stromal cells for cell-based therapy: Current status of preclinical studies and clinical trials. Curr. Opin. Mol. Ther. 2010, 12, 442–449. [Google Scholar]
- Ruetze, M.; Richter, W. Adipose-derived stromal cells for osteoarticular repair: Trophic function versus stem cell activity. Expert Rev. Mol. Med. 2014, 16, e9. [Google Scholar] [CrossRef] [PubMed]
- Im, W.; Ban, J.; Lim, J.; Lee, M.; Lee, S.T.; Chu, K.; Kim, M. Extracts of adipose derived stem cells slows progression in the R6/2 model of Huntington’s disease. PLoS ONE 2013, 8, e59438. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lataillade, J.J.; Doucet, C.; Bey, E.; Carsin, H.; Huet, C.; Clairand, I.; Bottollier-Depois, J.F.; Chapel, A.; Ernou, I.; Gourven, M.; et al. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen. Med. 2007, 2, 785–794. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bey, E.; Prat, M.; Duhamel, P.; Benderitter, M.; Brachet, M.; Trompier, F.; Battaglini, P.; Ernou, I.; Boutin, L.; Gourven, M.; et al. Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations. Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc. 2010, 18, 50–58. [Google Scholar] [CrossRef] [PubMed]
- Linard, C.; Brachet, M.; L’Homme, B.; Strup-Perrot, C.; Busson, E.; Bonneau, M.; Lataillade, J.J.; Bey, E.; Benderitter, M. Long-term effectiveness of local BM-MSCs for skeletal muscle regeneration: A proof of concept obtained on a pig model of severe radiation burn. Stem Cell Res. Ther. 2018, 9, 299. [Google Scholar] [CrossRef] [Green Version]
- Linard, C.; Busson, E.; Holler, V.; Strup-Perrot, C.; Lacave-Lapalun, J.V.; Lhomme, B.; Prat, M.; Devauchelle, P.; Sabourin, J.C.; Simon, J.M.; et al. Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs. Stem Cells Transl. Med. 2013, 2, 916–927. [Google Scholar] [CrossRef]
- Fortunel, N.O.; Chadli, L.; Coutier, J.; Lemaitre, G.; Auvre, F.; Domingues, S.; Bouissou-Cadio, E.; Vaigot, P.; Cavallero, S.; Deleuze, J.F.; et al. KLF4 inhibition promotes the expansion of keratinocyte precursors from adult human skin and of embryonic-stem-cell-derived keratinocytes. Nat. Biomed. Eng. 2019, 3, 985–997. [Google Scholar] [CrossRef]
- Ankrum, J.; Karp, J.M. Mesenchymal stem cell therapy: Two steps forward, one step back. Trends Mol. Med. 2010, 16, 203–209. [Google Scholar] [CrossRef] [Green Version]
- Ning, H.; Yang, F.; Jiang, M.; Hu, L.; Feng, K.; Zhang, J.; Yu, Z.; Li, B.; Xu, C.; Li, Y.; et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: Outcome of a pilot clinical study. Leukemia 2008, 22, 593–599. [Google Scholar] [CrossRef] [Green Version]
- Sundin, M.; Orvell, C.; Rasmusson, I.; Sundberg, B.; Ringden, O.; Le Blanc, K. Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. Bone Marrow Transplant. 2006, 37, 1051–1059. [Google Scholar] [CrossRef]
- Pilehvar-Soltanahmadi, Y.; Nouri, M.; Martino, M.M.; Fattahi, A.; Alizadeh, E.; Darabi, M.; Rahmati-Yamchi, M.; Zarghami, N. Cytoprotection, proliferation and epidermal differentiation of adipose tissue-derived stem cells on emu oil based electrospun nanofibrous mat. Exp. Cell Res. 2017, 357, 192–201. [Google Scholar] [CrossRef] [PubMed]
- Nejati-Koshki, K.; Mortazavi, Y.; Pilehvar-Soltanahmadi, Y.; Sheoran, S.; Zarghami, N. An update on application of nanotechnology and stem cells in spinal cord injury regeneration. Biomed. Pharmacother. 2017, 90, 85–92. [Google Scholar] [CrossRef] [PubMed]
- Saei Arezoumand, K.; Alizadeh, E.; Pilehvar-Soltanahmadi, Y.; Esmaeillou, M.; Zarghami, N. An overview on different strategies for the stemness maintenance of MSCs. Artif. Cells Nanomed. Biotechnol. 2017, 45, 1255–1271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herberts, C.A.; Kwa, M.S.; Hermsen, H.P. Risk factors in the development of stem cell therapy. J. Transl. Med. 2011, 9, 29. [Google Scholar] [CrossRef] [Green Version]
- Lukomska, B.; Stanaszek, L.; Zuba-Surma, E.; Legosz, P.; Sarzynska, S.; Drela, K. Challenges and Controversies in Human Mesenchymal Stem Cell Therapy. Stem Cells Int. 2019, 2019, 9628536. [Google Scholar] [CrossRef] [Green Version]
- Celikkan, F.T.; Mungan, C.; Sucu, M.; Ulus, A.T.; Cinar, O.; Ili, E.G.; Can, A. Optimizing the transport and storage conditions of current Good Manufacturing Practice -grade human umbilical cord mesenchymal stromal cells for transplantation (HUC-HEART Trial). Cytotherapy 2019, 21, 64–75. [Google Scholar] [CrossRef]
- Filip, S.; Mokry, J.; Horacek, J.; English, D. Stem cells and the phenomena of plasticity and diversity: A limiting property of carcinogenesis. Stem Cells Dev. 2008, 17, 1031–1038. [Google Scholar] [CrossRef]
- Heslop, J.A.; Hammond, T.G.; Santeramo, I.; Tort Piella, A.; Hopp, I.; Zhou, J.; Baty, R.; Graziano, E.I.; Proto Marco, B.; Caron, A.; et al. Concise review: Workshop review: Understanding and assessing the risks of stem cell-based therapies. Stem Cells Transl. Med. 2015, 4, 389–400. [Google Scholar] [CrossRef]
- Rubio, D.; Garcia-Castro, J.; Martin, M.C.; de la Fuente, R.; Cigudosa, J.C.; Lloyd, A.C.; Bernad, A. Spontaneous human adult stem cell transformation. Cancer Res. 2005, 65, 3035–3039. [Google Scholar] [CrossRef] [Green Version]
- Karnoub, A.E.; Dash, A.B.; Vo, A.P.; Sullivan, A.; Brooks, M.W.; Bell, G.W.; Richardson, A.L.; Polyak, K.; Tubo, R.; Weinberg, R.A. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007, 449, 557–563. [Google Scholar] [CrossRef]
- Galleu, A.; Riffo-Vasquez, Y.; Trento, C.; Lomas, C.; Dolcetti, L.; Cheung, T.S.; von Bonin, M.; Barbieri, L.; Halai, K.; Ward, S.; et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci. Transl. Med. 2017, 9, eaam7828. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pereira, R.F.; O’Hara, M.D.; Laptev, A.V.; Halford, K.W.; Pollard, M.D.; Class, R.; Simon, D.; Livezey, K.; Prockop, D.J. Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc. Natl. Acad. Sci. USA 1998, 95, 1142–1147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, R.H.; Pulin, A.A.; Seo, M.J.; Kota, D.J.; Ylostalo, J.; Larson, B.L.; Semprun-Prieto, L.; Delafontaine, P.; Prockop, D.J. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009, 5, 54–63. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, J.; Dennis, J.E.; Muzic, R.F.; Lundberg, M.; Caplan, A.I. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs 2001, 169, 12–20. [Google Scholar] [CrossRef]
- Schrepfer, S.; Deuse, T.; Reichenspurner, H.; Fischbein, M.P.; Robbins, R.C.; Pelletier, M.P. Stem cell transplantation: The lung barrier. Transplant. Proc. 2007, 39, 573–576. [Google Scholar] [CrossRef]
- Hou, D.; Youssef, E.A.; Brinton, T.J.; Zhang, P.; Rogers, P.; Price, E.T.; Yeung, A.C.; Johnstone, B.H.; Yock, P.G.; March, K.L. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials. Circulation 2005, 112, I150–I156. [Google Scholar]
- Kidd, S.; Spaeth, E.; Dembinski, J.L.; Dietrich, M.; Watson, K.; Klopp, A.; Battula, V.L.; Weil, M.; Andreeff, M.; Marini, F.C. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009, 27, 2614–2623. [Google Scholar] [CrossRef] [Green Version]
- Murry, C.E.; Soonpaa, M.H.; Reinecke, H.; Nakajima, H.; Nakajima, H.O.; Rubart, M.; Pasumarthi, K.B.; Virag, J.I.; Bartelmez, S.H.; Poppa, V.; et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004, 428, 664–668. [Google Scholar] [CrossRef]
- Toma, C.; Wagner, W.R.; Bowry, S.; Schwartz, A.; Villanueva, F. Fate of culture-expanded mesenchymal stem cells in the microvasculature: In vivo observations of cell kinetics. Circ. Res. 2009, 104, 398–402. [Google Scholar] [CrossRef] [Green Version]
- Leiker, M.; Suzuki, G.; Iyer, V.S.; Canty, J.M., Jr.; Lee, T. Assessment of a nuclear affinity labeling method for tracking implanted mesenchymal stem cells. Cell Transplant. 2008, 17, 911–922. [Google Scholar] [CrossRef] [Green Version]
- Wang, L.; Deng, J.; Tian, W.; Xiang, B.; Yang, T.; Li, G.; Wang, J.; Gruwel, M.; Kashour, T.; Rendell, J.; et al. Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: An MR imaging study of rat hearts. Am. J. Physiol. Heart Circ. Physiol. 2009, 297, H1020–H1031. [Google Scholar] [CrossRef] [PubMed]
- Bayes-Genis, A.; Soler-Botija, C.; Farre, J.; Sepulveda, P.; Raya, A.; Roura, S.; Prat-Vidal, C.; Galvez-Monton, C.; Montero, J.A.; Buscher, D.; et al. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. J. Mol. Cell. Cardiol. 2010, 49, 771–780. [Google Scholar] [CrossRef] [PubMed]
- Mazo, M.; Planat-Benard, V.; Abizanda, G.; Pelacho, B.; Leobon, B.; Gavira, J.J.; Penuelas, I.; Cemborain, A.; Penicaud, L.; Laharrague, P.; et al. Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. Eur. J. Heart Fail. 2008, 10, 454–462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jin, K.; Greenberg, D.A. Tales of transdifferentiation. Exp. Neurol. 2003, 183, 255–257. [Google Scholar] [CrossRef]
- Togel, F.; Hu, Z.; Weiss, K.; Isaac, J.; Lange, C.; Westenfelder, C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am. J. Physiol. Ren. Physiol. 2005, 289, F31–F42. [Google Scholar] [CrossRef] [Green Version]
- Caplan, A.I.; Dennis, J.E. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. 2006, 98, 1076–1084. [Google Scholar] [CrossRef]
- Gnecchi, M.; He, H.; Noiseux, N.; Liang, O.D.; Zhang, L.; Morello, F.; Mu, H.; Melo, L.G.; Pratt, R.E.; Ingwall, J.S.; et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2006, 20, 661–669. [Google Scholar]
- Teixeira, F.G.; Carvalho, M.M.; Sousa, N.; Salgado, A.J. Mesenchymal stem cells secretome: A new paradigm for central nervous system regeneration? Cell. Mol. Life Sci. CMLS 2013, 70, 3871–3882. [Google Scholar] [CrossRef]
- Madrigal, M.; Rao, K.S.; Riordan, N.H. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J. Transl. Med. 2014, 12, 260. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Tredget, E.E.; Wu, P.Y.; Wu, Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS ONE 2008, 3, e1886. [Google Scholar] [CrossRef] [Green Version]
- Hung, S.C.; Pochampally, R.R.; Chen, S.C.; Hsu, S.C.; Prockop, D.J. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells 2007, 25, 2363–2370. [Google Scholar] [CrossRef] [PubMed]
- Togel, F.; Weiss, K.; Yang, Y.; Hu, Z.; Zhang, P.; Westenfelder, C. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am. J. Physiol. Ren. Physiol. 2007, 292, F1626–F1635. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- van Poll, D.; Parekkadan, B.; Cho, C.H.; Berthiaume, F.; Nahmias, Y.; Tilles, A.W.; Yarmush, M.L. Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 2008, 47, 1634–1643. [Google Scholar] [CrossRef]
- Uemura, R.; Xu, M.; Ahmad, N.; Ashraf, M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ. Res. 2006, 98, 1414–1421. [Google Scholar] [CrossRef] [Green Version]
- Cunningham, C.J.; Redondo-Castro, E.; Allan, S.M. The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke. J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 2018, 38, 1276–1292. [Google Scholar] [CrossRef] [Green Version]
- Yang, Y.; Lin, H.; Shen, H.; Wang, B.; Lei, G.; Tuan, R.S. Mesenchymal stem cell-derived extracellular matrix enhances chondrogenic phenotype of and cartilage formation by encapsulated chondrocytes in vitro and in vivo. Acta Biomater. 2018, 69, 71–82. [Google Scholar] [CrossRef]
- Beer, L.; Mildner, M.; Ankersmit, H.J. Cell secretome based drug substances in regenerative medicine: When regulatory affairs meet basic science. Ann. Transl. Med. 2017, 5, 170. [Google Scholar] [CrossRef] [Green Version]
- Gnecchi, M.; Danieli, P.; Malpasso, G.; Ciuffreda, M.C. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair. Methods Mol. Biol. 2016, 1416, 123–146. [Google Scholar]
- Liu, L.; Gao, J.; Yuan, Y.; Chang, Q.; Liao, Y.; Lu, F. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF. Cell Biol. Int. 2013, 37, 551–560. [Google Scholar] [CrossRef]
- Tasso, R.; Gaetani, M.; Molino, E.; Cattaneo, A.; Monticone, M.; Bachi, A.; Cancedda, R. The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model. Biomaterials 2012, 33, 2086–2096. [Google Scholar] [CrossRef]
- Magne, B.; Dedier, M.; Nivet, M.; Coulomb, B.; Banzet, S.; Lataillade, J.J.; Trouillas, M. IL-1beta-Primed Mesenchymal Stromal Cells Improve Epidermal Substitute Engraftment and Wound Healing via Matrix Metalloproteinases and Transforming Growth Factor-beta1. J. Investig. Dermatol. 2020, 140, 688–698 e621. [Google Scholar] [CrossRef] [PubMed]
- Witwer, K.W.; Van Balkom, B.W.M.; Bruno, S.; Choo, A.; Dominici, M.; Gimona, M.; Hill, A.F.; De Kleijn, D.; Koh, M.; Lai, R.C.; et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J. Extracell. Vesicles 2019, 8, 1609206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mathivanan, S.; Ji, H.; Simpson, R.J. Exosomes: Extracellular organelles important in intercellular communication. J. Proteom. 2010, 73, 1907–1920. [Google Scholar] [CrossRef] [PubMed]
- Behnke, O. Electron microscopical observations on the surface coating of human blood platelets. J. Ultrastruct. Res. 1968, 24, 51–69. [Google Scholar] [CrossRef]
- Chargaff, E.; West, R. The biological significance of the thromboplastic protein of blood. J. Biol. Chem. 1946, 166, 189–197. [Google Scholar] [PubMed]
- Keller, S.; Ridinger, J.; Rupp, A.K.; Janssen, J.W.; Altevogt, P. Body fluid derived exosomes as a novel template for clinical diagnostics. J. Transl. Med. 2011, 9, 86. [Google Scholar] [CrossRef] [Green Version]
- Caby, M.P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 2005, 17, 879–887. [Google Scholar] [CrossRef] [Green Version]
- Thery, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 2006, 30, 3–22. [Google Scholar] [CrossRef]
- Colombo, M.; Raposo, G.; Thery, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014, 30, 255–289. [Google Scholar] [CrossRef]
- Turturici, G.; Tinnirello, R.; Sconzo, G.; Geraci, F. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: Advantages and disadvantages. Am. J. Physiol. Cell Physiol. 2014, 306, C621–C633. [Google Scholar] [CrossRef] [Green Version]
- Kowal, J.; Arras, G.; Colombo, M.; Jouve, M.; Morath, J.P.; Primdal-Bengtson, B.; Dingli, F.; Loew, D.; Tkach, M.; Thery, C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc. Natl. Acad. Sci. USA 2016, 113, E968–E977. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taylor, D.D.; Homesley, H.D.; Doellgast, G.J. Binding of specific peroxidase-labeled antibody to placental-type phosphatase on tumor-derived membrane fragments. Cancer Res. 1980, 40, 4064–4069. [Google Scholar] [PubMed]
- Minciacchi, V.R.; Freeman, M.R.; Di Vizio, D. Extracellular vesicles in cancer: Exosomes, microvesicles and the emerging role of large oncosomes. Semin. Cell Dev. Biol. 2015, 40, 41–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ratajczak, J.; Wysoczynski, M.; Hayek, F.; Janowska-Wieczorek, A.; Ratajczak, M.Z. Membrane-derived microvesicles: Important and underappreciated mediators of cell-to-cell communication. Leukemia 2006, 20, 1487–1495. [Google Scholar] [CrossRef]
- Moskovich, O.; Fishelson, Z. Live cell imaging of outward and inward vesiculation induced by the complement c5b-9 complex. J. Biol. Chem. 2007, 282, 29977–29986. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gyorgy, B.; Szabo, T.G.; Pasztoi, M.; Pal, Z.; Misjak, P.; Aradi, B.; Laszlo, V.; Pallinger, E.; Pap, E.; Kittel, A.; et al. Membrane vesicles, current state-of-the-art: Emerging role of extracellular vesicles. Cell. Mol. Life Sci. CMLS 2011, 68, 2667–2688. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wiklander, O.P.B.; Brennan, M.A.; Lotvall, J.; Breakefield, X.O.; El Andaloussi, S. Advances in therapeutic applications of extracellular vesicles. Sci. Transl. Med. 2019, 11, eaav8521. [Google Scholar] [CrossRef]
- Dias, I.E.; Pinto, P.O.; Barros, L.C.; Viegas, C.A.; Dias, I.R.; Carvalho, P.P. Mesenchymal stem cells therapy in companion animals: Useful for immune-mediated diseases? BMC Vet. Res. 2019, 15, 358. [Google Scholar] [CrossRef] [Green Version]
- Thery, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. 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 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Hauser, P.; Wang, S.; Didenko, V.V. Apoptotic Bodies: Selective Detection in Extracellular Vesicles. Methods Mol. Biol. 2017, 1554, 193–200. [Google Scholar]
- Gregory, C.D.; Dransfield, I. Apoptotic Tumor Cell-Derived Extracellular Vesicles as Important Regulators of the Onco-Regenerative Niche. Front. Immunol. 2018, 9, 1111. [Google Scholar] [CrossRef] [Green Version]
- Hinger, S.A.; Cha, D.J.; Franklin, J.L.; Higginbotham, J.N.; Dou, Y.; Ping, J.; Shu, L.; Prasad, N.; Levy, S.; Zhang, B.; et al. Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells. Cell Rep. 2018, 25, 715–725 e714. [Google Scholar] [CrossRef] [Green Version]
- Sharma, H.; Chinnappan, M.; Agarwal, S.; Dalvi, P.; Gunewardena, S.; O’Brien-Ladner, A.; Dhillon, N.K. Macrophage-derived extracellular vesicles mediate smooth muscle hyperplasia: Role of altered miRNA cargo in response to HIV infection and substance abuse. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2018, 32, 5174–5185. [Google Scholar] [CrossRef]
- Cocucci, E.; Racchetti, G.; Podini, P.; Meldolesi, J. Enlargeosome traffic: Exocytosis triggered by various signals is followed by endocytosis, membrane shedding or both. Traffic 2007, 8, 742–757. [Google Scholar] [CrossRef]
- Li, C.C.; Eaton, S.A.; Young, P.E.; Lee, M.; Shuttleworth, R.; Humphreys, D.T.; Grau, G.E.; Combes, V.; Bebawy, M.; Gong, J.; et al. Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol. 2013, 10, 1333–1344. [Google Scholar] [CrossRef] [Green Version]
- Gasser, O.; Schifferli, J.A. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 2004, 104, 2543–2548. [Google Scholar] [CrossRef] [PubMed]
- Janowska-Wieczorek, A.; Majka, M.; Kijowski, J.; Baj-Krzyworzeka, M.; Reca, R.; Turner, A.R.; Ratajczak, J.; Emerson, S.G.; Kowalska, M.A.; Ratajczak, M.Z. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 2001, 98, 3143–3149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morel, O.; Toti, F.; Hugel, B.; Freyssinet, J.M. Cellular microparticles: A disseminated storage pool of bioactive vascular effectors. Curr. Opin. Hematol. 2004, 11, 156–164. [Google Scholar] [CrossRef] [PubMed]
- Kupcova Skalnikova, H. Proteomic techniques for characterisation of mesenchymal stem cell secretome. Biochimie 2013, 95, 2196–2211. [Google Scholar] [CrossRef]
- Candela, M.E.; Geraci, F.; Turturici, G.; Taverna, S.; Albanese, I.; Sconzo, G. Membrane vesicles containing matrix metalloproteinase-9 and fibroblast growth factor-2 are released into the extracellular space from mouse mesoangioblast stem cells. J. Cell. Physiol. 2010, 224, 144–151. [Google Scholar] [CrossRef]
- MacKenzie, A.; Wilson, H.L.; Kiss-Toth, E.; Dower, S.K.; North, R.A.; Surprenant, A. Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 2001, 15, 825–835. [Google Scholar] [CrossRef]
- Lai, R.C.; Tan, S.S.; Teh, B.J.; Sze, S.K.; Arslan, F.; de Kleijn, D.P.; Choo, A.; Lim, S.K. Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome. Int. J. Proteom. 2012, 2012, 971907. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.S.; Choi, D.Y.; Yun, S.J.; Choi, S.M.; Kang, J.W.; Jung, J.W.; Hwang, D.; Kim, K.P.; Kim, D.W. Proteomic analysis of microvesicles derived from human mesenchymal stem cells. J. Proteome Res. 2012, 11, 839–849. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.K.; Lee, J.; Kim, S.R.; Choi, D.S.; Yoon, Y.J.; Kim, J.H.; Go, G.; Nhung, D.; Hong, K.; Jang, S.C.; et al. EVpedia: A community web portal for extracellular vesicles research. Bioinformatics 2015, 31, 933–939. [Google Scholar] [CrossRef]
- Simpson, R.J.; Kalra, H.; Mathivanan, S. ExoCarta as a resource for exosomal research. J. Extracell. Vesicles 2012, 1. [Google Scholar] [CrossRef]
- Mathivanan, S.; Fahner, C.J.; Reid, G.E.; Simpson, R.J. ExoCarta 2012: Database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012, 40, D1241–D1244. [Google Scholar] [CrossRef] [Green Version]
- Hsiao, S.T.; Asgari, A.; Lokmic, Z.; Sinclair, R.; Dusting, G.J.; Lim, S.Y.; Dilley, R.J. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2012, 21, 2189–2203. [Google Scholar] [CrossRef] [Green Version]
- Eirin, A.; Zhu, X.Y.; Puranik, A.S.; Woollard, J.R.; Tang, H.; Dasari, S.; Lerman, A.; van Wijnen, A.J.; Lerman, L.O. Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells. Sci. Rep. 2016, 6, 36120. [Google Scholar] [CrossRef]
- Eirin, A.; Zhu, X.Y.; Puranik, A.S.; Tang, H.; McGurren, K.A.; van Wijnen, A.J.; Lerman, A.; Lerman, L.O. Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. Kidney Int. 2017, 92, 114–124. [Google Scholar] [CrossRef]
- Aliotta, J.M.; Pereira, M.; Johnson, K.W.; de Paz, N.; Dooner, M.S.; Puente, N.; Ayala, C.; Brilliant, K.; Berz, D.; Lee, D.; et al. Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription. Exp. Hematol. 2010, 38, 233–245. [Google Scholar] [CrossRef] [Green Version]
- Camussi, G.; Deregibus, M.C.; Bruno, S.; Grange, C.; Fonsato, V.; Tetta, C. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am. J. Cancer Res. 2011, 1, 98–110. [Google Scholar] [PubMed]
- Camussi, G.; Deregibus, M.C.; Tetta, C. Paracrine/endocrine mechanism of stem cells on kidney repair: Role of microvesicle-mediated transfer of genetic information. Curr. Opin. Nephrol. Hypertens. 2010, 19, 7–12. [Google Scholar] [CrossRef] [PubMed]
- Yanez-Mo, M.; Siljander, P.R.; Andreu, Z.; Zavec, A.B.; Borras, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krol, J.; Loedige, I.; Filipowicz, W. The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet. 2010, 11, 597–610. [Google Scholar] [CrossRef]
- Ma, T.; Chen, Y.; Chen, Y.; Meng, Q.; Sun, J.; Shao, L.; Yu, Y.; Huang, H.; Hu, Y.; Yang, Z.; et al. MicroRNA-132, Delivered by Mesenchymal Stem Cell-Derived Exosomes, Promote Angiogenesis in Myocardial Infarction. Stem Cells Int. 2018, 2018, 3290372. [Google Scholar] [CrossRef] [Green Version]
- Zhang, J.; Li, S.; Li, L.; Li, M.; Guo, C.; Yao, J.; Mi, S. Exosome and exosomal microRNA: Trafficking, sorting, and function. Genom. Proteom. Bioinform. 2015, 13, 17–24. [Google Scholar] [CrossRef] [Green Version]
- Salinas-Vera, Y.M.; Marchat, L.A.; Gallardo-Rincon, D.; Ruiz-Garcia, E.; Astudillo-De La Vega, H.; Echavarria-Zepeda, R.; Lopez-Camarillo, C. AngiomiRs: MicroRNAs driving angiogenesis in cancer (Review). Int. J. Mol. Med. 2019, 43, 657–670. [Google Scholar] [CrossRef] [Green Version]
- Liang, X.; Zhang, L.; Wang, S.; Han, Q.; Zhao, R.C. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J. Cell Sci. 2016, 129, 2182–2189. [Google Scholar] [CrossRef] [Green Version]
- Baglio, S.R.; Rooijers, K.; Koppers-Lalic, D.; Verweij, F.J.; Perez Lanzon, M.; Zini, N.; Naaijkens, B.; Perut, F.; Niessen, H.W.; Baldini, N.; et al. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res. Ther. 2015, 6, 127. [Google Scholar] [CrossRef] [Green Version]
- De Luca, L.; Trino, S.; Laurenzana, I.; Simeon, V.; Calice, G.; Raimondo, S.; Podesta, M.; Santodirocco, M.; Di Mauro, L.; La Rocca, F.; et al. MiRNAs and piRNAs from bone marrow mesenchymal stem cell extracellular vesicles induce cell survival and inhibit cell differentiation of cord blood hematopoietic stem cells: A new insight in transplantation. Oncotarget 2016, 7, 6676–6692. [Google Scholar] [CrossRef] [Green Version]
- Fatima, F.; Nawaz, M. Vesiculated Long Non-Coding RNAs: Offshore Packages Deciphering Trans-Regulation between Cells, Cancer Progression and Resistance to Therapies. Non-Coding RNA 2017, 3, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, D.S.; Kim, D.K.; Kim, Y.K.; Gho, Y.S. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics 2013, 13, 1554–1571. [Google Scholar] [CrossRef] [PubMed]
- Deng, H.; Sun, C.; Sun, Y.; Li, H.; Yang, L.; Wu, D.; Gao, Q.; Jiang, X. Lipid, Protein, and MicroRNA Composition Within Mesenchymal Stem Cell-Derived Exosomes. Cell. Reprogramming 2018, 20, 178–186. [Google Scholar] [CrossRef] [PubMed]
- Xiang, C.; Yang, K.; Liang, Z.; Wan, Y.; Cheng, Y.; Ma, D.; Zhang, H.; Hou, W.; Fu, P. Sphingosine-1-phosphate mediates the therapeutic effects of bone marrow mesenchymal stem cell-derived microvesicles on articular cartilage defect. Transl. Res. J. Lab. Clin. Med. 2018, 193, 42–53. [Google Scholar] [CrossRef]
- Miyanishi, M.; Tada, K.; Koike, M.; Uchiyama, Y.; Kitamura, T.; Nagata, S. Identification of Tim4 as a phosphatidylserine receptor. Nature 2007, 450, 435–439. [Google Scholar] [CrossRef] [Green Version]
- Yang, D.; Wang, W.; Li, L.; Peng, Y.; Chen, P.; Huang, H.; Guo, Y.; Xia, X.; Wang, Y.; Wang, H.; et al. The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS ONE 2013, 8, e59020. [Google Scholar] [CrossRef]
- Salgado, A.J.; Reis, R.L.; Sousa, N.J.; Gimble, J.M. Adipose tissue derived stem cells secretome: Soluble factors and their roles in regenerative medicine. Curr. Stem Cell Res. Ther. 2010, 5, 103–110. [Google Scholar] [CrossRef] [Green Version]
- Drago, D.; Cossetti, C.; Iraci, N.; Gaude, E.; Musco, G.; Bachi, A.; Pluchino, S. The stem cell secretome and its role in brain repair. Biochimie 2013, 95, 2271–2285. [Google Scholar] [CrossRef] [Green Version]
- Yin, L.; Liu, X.; Shi, Y.; Ocansey, D.K.W.; Hu, Y.; Li, X.; Zhang, C.; Xu, W.; Qian, H. Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine. Cells 2020, 9, 707. [Google Scholar] [CrossRef] [Green Version]
- Zhang, B.; Tian, X.; Hao, J.; Xu, G.; Zhang, W. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration. Cell Transplant. 2020, 29, 963689720908500. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.; Mitsialis, S.A.; Aslam, M.; Vitali, S.H.; Vergadi, E.; Konstantinou, G.; Sdrimas, K.; Fernandez-Gonzalez, A.; Kourembanas, S. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation 2012, 126, 2601–2611. [Google Scholar] [CrossRef] [Green Version]
- Aliotta, J.M.; Pereira, M.; Wen, S.; Dooner, M.S.; Del Tatto, M.; Papa, E.; Goldberg, L.R.; Baird, G.L.; Ventetuolo, C.E.; Quesenberry, P.J.; et al. Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice. Cardiovasc. Res. 2016, 110, 319–330. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tang, X.D.; Shi, L.; Monsel, A.; Li, X.Y.; Zhu, H.L.; Zhu, Y.G.; Qu, J.M. Mesenchymal Stem Cell Microvesicles Attenuate Acute Lung Injury in Mice Partly Mediated by Ang-1 mRNA. Stem Cells 2017, 35, 1849–1859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Potter, D.R.; Miyazawa, B.Y.; Gibb, S.L.; Deng, X.; Togaratti, P.P.; Croze, R.H.; Srivastava, A.K.; Trivedi, A.; Matthay, M.; Holcomb, J.B.; et al. Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma. J. Trauma Acute Care Surg. 2018, 84, 245–256. [Google Scholar] [CrossRef] [PubMed]
- Gatti, S.; Bruno, S.; Deregibus, M.C.; Sordi, A.; Cantaluppi, V.; Tetta, C.; Camussi, G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. Eur. Ren. Assoc. 2011, 26, 1474–1483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bruno, S.; Grange, C.; Collino, F.; Deregibus, M.C.; Cantaluppi, V.; Biancone, L.; Tetta, C.; Camussi, G. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS ONE 2012, 7, e33115. [Google Scholar] [CrossRef] [PubMed]
- Bruno, S.; Tapparo, M.; Collino, F.; Chiabotto, G.; Deregibus, M.C.; Soares Lindoso, R.; Neri, F.; Kholia, S.; Giunti, S.; Wen, S.; et al. Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells. Tissue Eng. A 2017, 23, 1262–1273. [Google Scholar] [CrossRef] [PubMed]
- Zou, X.; Gu, D.; Xing, X.; Cheng, Z.; Gong, D.; Zhang, G.; Zhu, Y. Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats. Am. J. Transl. Res. 2016, 8, 4289–4299. [Google Scholar]
- Zou, X.; Zhang, G.; Cheng, Z.; Yin, D.; Du, T.; Ju, G.; Miao, S.; Liu, G.; Lu, M.; Zhu, Y. Microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells ameliorate renal ischemia-reperfusion injury in rats by suppressing CX3CL1. Stem Cell Res. Ther. 2014, 5, 40. [Google Scholar] [CrossRef] [Green Version]
- He, J.; Wang, Y.; Lu, X.; Zhu, B.; Pei, X.; Wu, J.; Zhao, W. Micro-vesicles derived from bone marrow stem cells protect the kidney both in vivo and in vitro by microRNA-dependent repairing. Nephrology 2015, 20, 591–600. [Google Scholar] [CrossRef]
- He, J.; Wang, Y.; Sun, S.; Yu, M.; Wang, C.; Pei, X.; Zhu, B.; Wu, J.; Zhao, W. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology 2012, 17, 493–500. [Google Scholar] [CrossRef] [PubMed]
- Choi, H.Y.; Lee, H.G.; Kim, B.S.; Ahn, S.H.; Jung, A.; Lee, M.; Lee, J.E.; Kim, H.J.; Ha, S.K.; Park, H.C. Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction. Stem Cell Res. Ther. 2015, 6, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eirin, A.; Zhu, X.Y.; Puranik, A.S.; Woollard, J.R.; Tang, H.; Dasari, S.; Lerman, A.; van Wijnen, A.J.; Lerman, L.O. Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells. PLoS ONE 2017, 12, e0174303. [Google Scholar] [CrossRef] [PubMed]
- Shen, B.; Liu, J.; Zhang, F.; Wang, Y.; Qin, Y.; Zhou, Z.; Qiu, J.; Fan, Y. CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury. Stem Cells Int. 2016, 2016, 1240301. [Google Scholar] [CrossRef] [Green Version]
- Jia, H.; Liu, W.; Zhang, B.; Wang, J.; Wu, P.; Tandra, N.; Liang, Z.; Ji, C.; Yin, L.; Hu, X.; et al. HucMSC exosomes-delivered 14-3-3zeta enhanced autophagy via modulation of ATG16L in preventing cisplatin-induced acute kidney injury. Am. J. Transl. Res. 2018, 10, 101–113. [Google Scholar]
- Wang, B.; Jia, H.; Zhang, B.; Wang, J.; Ji, C.; Zhu, X.; Yan, Y.; Yin, L.; Yu, J.; Qian, H.; et al. Pre-incubation with hucMSC-exosomes prevents cisplatin-induced nephrotoxicity by activating autophagy. Stem Cell Res. Ther. 2017, 8, 75. [Google Scholar] [CrossRef] [Green Version]
- Lai, R.C.; Arslan, F.; Lee, M.M.; Sze, N.S.; Choo, A.; Chen, T.S.; Salto-Tellez, M.; Timmers, L.; Lee, C.N.; El Oakley, R.M.; et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010, 4, 214–222. [Google Scholar] [CrossRef] [Green Version]
- Shao, L.; Zhang, Y.; Lan, B.; Wang, J.; Zhang, Z.; Zhang, L.; Xiao, P.; Meng, Q.; Geng, Y.J.; Yu, X.Y.; et al. MiRNA-Sequence Indicates That Mesenchymal Stem Cells and Exosomes Have Similar Mechanism to Enhance Cardiac Repair. BioMed Res. Int. 2017, 2017, 4150705. [Google Scholar] [CrossRef]
- Pan, W.; Zhu, Y.; Meng, X.; Zhang, C.; Yang, Y.; Bei, Y. Immunomodulation by Exosomes in Myocardial Infarction. J. Cardiovasc. Transl. Res. 2019, 12, 28–36. [Google Scholar] [CrossRef]
- Teng, X.; Chen, L.; Chen, W.; Yang, J.; Yang, Z.; Shen, Z. Mesenchymal Stem Cell-Derived Exosomes Improve the Microenvironment of Infarcted Myocardium Contributing to Angiogenesis and Anti-Inflammation. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2015, 37, 2415–2424. [Google Scholar] [CrossRef]
- Arslan, F.; Lai, R.C.; Smeets, M.B.; Akeroyd, L.; Choo, A.; Aguor, E.N.; Timmers, L.; van Rijen, H.V.; Doevendans, P.A.; Pasterkamp, G.; et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 2013, 10, 301–312. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, M.; Wang, H.; Jin, M.; Yang, X.; Ji, H.; Jiang, Y.; Zhang, H.; Wu, F.; Wu, G.; Lai, X.; et al. Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2018, 47, 864–878. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Sun, X.; Cao, W.; Ma, J.; Sun, L.; Qian, H.; Zhu, W.; Xu, W. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury. Stem Cells Int. 2015, 2015, 761643. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Sun, X.; Gong, X.; Wang, G. Human umbilical cord mesenchymal stem cells derived exosomes exert antiapoptosis effect via activating PI3K/Akt/mTOR pathway on H9C2 cells. J. Cell. Biochem. 2019, 120, 14455–14464. [Google Scholar] [CrossRef]
- Vrijsen, K.R.; Maring, J.A.; Chamuleau, S.A.; Verhage, V.; Mol, E.A.; Deddens, J.C.; Metz, C.H.; Lodder, K.; van Eeuwijk, E.C.; van Dommelen, S.M.; et al. Exosomes from Cardiomyocyte Progenitor Cells and Mesenchymal Stem Cells Stimulate Angiogenesis Via EMMPRIN. Adv. Healthc. Mater. 2016, 5, 2555–2565. [Google Scholar] [CrossRef]
- Wang, N.; Chen, C.; Yang, D.; Liao, Q.; Luo, H.; Wang, X.; Zhou, F.; Yang, X.; Yang, J.; Zeng, C.; et al. Mesenchymal stem cells-derived extracellular vesicles, via miR-210, improve infarcted cardiac function by promotion of angiogenesis. Biochim. Biophys. Acta Mol. Basis Dis. 2017, 1863, 2085–2092. [Google Scholar] [CrossRef]
- Luther, K.M.; Haar, L.; McGuinness, M.; Wang, Y.; Lynch Iv, T.L.; Phan, A.; Song, Y.; Shen, Z.; Gardner, G.; Kuffel, G.; et al. Exosomal miR-21a-5p mediates cardioprotection by mesenchymal stem cells. J. Mol. Cell. Cardiol. 2018, 119, 125–137. [Google Scholar] [CrossRef]
- Wang, K.; Jiang, Z.; Webster, K.A.; Chen, J.; Hu, H.; Zhou, Y.; Zhao, J.; Wang, L.; Wang, Y.; Zhong, Z.; et al. Enhanced Cardioprotection by Human Endometrium Mesenchymal Stem Cells Driven by Exosomal MicroRNA-21. Stem Cells Transl. Med. 2017, 6, 209–222. [Google Scholar] [CrossRef]
- Xiao, C.; Wang, K.; Xu, Y.; Hu, H.; Zhang, N.; Wang, Y.; Zhong, Z.; Zhao, J.; Li, Q.; Zhu, D.; et al. Transplanted Mesenchymal Stem Cells Reduce Autophagic Flux in Infarcted Hearts via the Exosomal Transfer of miR-125b. Circ. Res. 2018, 123, 564–578. [Google Scholar] [CrossRef]
- Liu, J.; Jiang, M.; Deng, S.; Lu, J.; Huang, H.; Zhang, Y.; Gong, P.; Shen, X.; Ruan, H.; Jin, M.; et al. miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage. Mol. Ther. Nucleic Acids 2018, 11, 103–115. [Google Scholar] [CrossRef] [Green Version]
- Luo, Q.; Guo, D.; Liu, G.; Chen, G.; Hang, M.; Jin, M. Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2017, 44, 2105–2116. [Google Scholar]
- Phinney, D.G.; Pittenger, M.F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells 2017, 35, 851–858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Doeppner, T.R.; Herz, J.; Gorgens, A.; Schlechter, J.; Ludwig, A.K.; Radtke, S.; de Miroschedji, K.; Horn, P.A.; Giebel, B.; Hermann, D.M. Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression. Stem Cells Transl. Med. 2015, 4, 1131–1143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moon, G.J.; Sung, J.H.; Kim, D.H.; Kim, E.H.; Cho, Y.H.; Son, J.P.; Cha, J.M.; Bang, O.Y. Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study. Transl. Stroke Res. 2019, 10, 509–521. [Google Scholar] [CrossRef]
- Chuang, T.J.; Lin, K.C.; Chio, C.C.; Wang, C.C.; Chang, C.P.; Kuo, J.R. Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats. J. Trauma Acute Care Surg. 2012, 73, 1161–1167. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Chopp, M.; Meng, Y.; Katakowski, M.; Xin, H.; Mahmood, A.; Xiong, Y. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J. Neurosurg. 2015, 122, 856–867. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, D.K.; Nishida, H.; An, S.Y.; Shetty, A.K.; Bartosh, T.J.; Prockop, D.J. Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc. Natl. Acad. Sci. USA 2016, 113, 170–175. [Google Scholar] [CrossRef] [Green Version]
- Patel, N.A.; Moss, L.D.; Lee, J.Y.; Tajiri, N.; Acosta, S.; Hudson, C.; Parag, S.; Cooper, D.R.; Borlongan, C.V.; Bickford, P.C. Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury. J. Neuroinflammation 2018, 15, 204. [Google Scholar] [CrossRef] [Green Version]
- Nerem, R.M. Cell-based therapies: From basic biology to replacement, repair, and regeneration. Biomaterials 2007, 28, 5074–5077. [Google Scholar] [CrossRef]
- Shiue, S.J.; Rau, R.H.; Shiue, H.S.; Hung, Y.W.; Li, Z.X.; Yang, K.D.; Cheng, J.K. Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats. Pain 2019, 160, 210–223. [Google Scholar] [CrossRef]
- Sun, G.; Li, G.; Li, D.; Huang, W.; Zhang, R.; Zhang, H.; Duan, Y.; Wang, B. hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 89, 194–204. [Google Scholar] [CrossRef]
- Wang, L.; Pei, S.; Han, L.; Guo, B.; Li, Y.; Duan, R.; Yao, Y.; Xue, B.; Chen, X.; Jia, Y. Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFkappaB P65 Subunit in Spinal Cord Injury. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2018, 50, 1535–1559. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.M.; Gibbs, K.M.; Davila, J.; Campbell, N.; Sung, S.; Todorova, T.I.; Otsuka, S.; Sabaawy, H.E.; Hart, R.P.; Schachner, M. MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. Eur. J. Neurosci. 2011, 33, 1587–1597. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lener, T.; Gimona, M.; Aigner, L.; Borger, V.; Buzas, E.; Camussi, G.; Chaput, N.; Chatterjee, D.; Court, F.A.; Del Portillo, H.A.; et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J. Extracell. Vesicles 2015, 4, 30087. [Google Scholar] [CrossRef] [PubMed]
- Lelek, J.; Zuba-Surma, E.K. Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies-Synthetic Review. Int. J. Mol. Sci. 2020, 21, 799. [Google Scholar] [CrossRef] [Green Version]
- Abbaszadeh, H.; Ghorbani, F.; Derakhshani, M.; Movassaghpour, A.; Yousefi, M. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm. J. Cell. Physiol. 2020, 235, 706–717. [Google Scholar] [CrossRef]
- Hughes, C.S.; Nuhn, A.A.; Postovit, L.M.; Lajoie, G.A. Proteomics of human embryonic stem cells. Proteomics 2011, 11, 675–690. [Google Scholar] [CrossRef]
- Baharvand, H.; Hajheidari, M.; Ashtiani, S.K.; Salekdeh, G.H. Proteomic signature of human embryonic stem cells. Proteomics 2006, 6, 3544–3549. [Google Scholar] [CrossRef]
- Ong, S.G.; Lee, W.H.; Huang, M.; Dey, D.; Kodo, K.; Sanchez-Freire, V.; Gold, J.D.; Wu, J.C. Cross talk of combined gene and cell therapy in ischemic heart disease: Role of exosomal microRNA transfer. Circulation 2014, 130, S60–S69. [Google Scholar] [CrossRef] [Green Version]
- Feng, Y.; Huang, W.; Wani, M.; Yu, X.; Ashraf, M. Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22. PLoS ONE 2014, 9, e88685. [Google Scholar] [CrossRef]
- Wang, Y.; Zhang, L.; Li, Y.; Chen, L.; Wang, X.; Guo, W.; Zhang, X.; Qin, G.; He, S.H.; Zimmerman, A.; et al. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int. J. Cardiol. 2015, 192, 61–69. [Google Scholar] [CrossRef] [Green Version]
- Xuan, W.; Wang, L.; Xu, M.; Weintraub, N.L.; Ashraf, M. miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart. Stem Cells Int. 2019, 2019, 3726392. [Google Scholar] [CrossRef] [PubMed]
- Wei, F.; Cao, C.; Xu, X.; Wang, J. Diverse functions of miR-373 in cancer. J. Transl. Med. 2015, 13, 162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oh, M.; Lee, J.; Kim, Y.J.; Rhee, W.J.; Park, J.H. Exosomes Derived from Human Induced Pluripotent Stem Cells Ameliorate the Aging of Skin Fibroblasts. Int. J. Mol. Sci. 2018, 19, 1715. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, P.Y.; Chien, Y.; Chiou, G.Y.; Lin, C.H.; Chiou, C.H.; Tarng, D.C. Induced pluripotent stem cells without c-Myc attenuate acute kidney injury via downregulating the signaling of oxidative stress and inflammation in ischemia-reperfusion rats. Cell Transplant. 2012, 21, 2569–2585. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Collino, F.; Lopes, J.A.; Tapparo, M.; Tortelote, G.G.; Kasai-Brunswick, T.H.; Lopes, G.M.C.; Almeida, D.B.; Skovronova, R.; Wendt, C.H.C.; Miranda, K.R.; et al. Extracellular Vesicles Derived from Induced Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model. Cells 2020, 9, 453. [Google Scholar] [CrossRef] [Green Version]
- Gazdhar, A.; Grad, I.; Tamo, L.; Gugger, M.; Feki, A.; Geiser, T. The secretome of induced pluripotent stem cells reduces lung fibrosis in part by hepatocyte growth factor. Stem Cell Res. Ther. 2014, 5, 123. [Google Scholar] [CrossRef] [Green Version]
- Zhang, G.; Chen, L.; Guo, X.; Wang, H.; Chen, W.; Wu, G.; Gu, B.; Miao, W.; Kong, J.; Jin, X.; et al. Comparative Analysis of microRNA Expression Profiles of Exosomes Derived from Normal and Hypoxic Preconditioning Human Neural Stem Cells by Next Generation Sequencing. J. Biomed. Nanotechnol. 2018, 14, 1075–1089. [Google Scholar] [CrossRef]
- Gray, W.D.; French, K.M.; Ghosh-Choudhary, S.; Maxwell, J.T.; Brown, M.E.; Platt, M.O.; Searles, C.D.; Davis, M.E. Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ. Res. 2015, 116, 255–263. [Google Scholar] [CrossRef] [Green Version]
- Xiao, J.; Pan, Y.; Li, X.H.; Yang, X.Y.; Feng, Y.L.; Tan, H.H.; Jiang, L.; Feng, J.; Yu, X.Y. Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death Dis. 2016, 7, e2277. [Google Scholar] [CrossRef] [Green Version]
- Han, C.; Zhou, J.; Liu, B.; Liang, C.; Pan, X.; Zhang, Y.; Zhang, Y.; Wang, Y.; Shao, L.; Zhu, B.; et al. Delivery of miR-675 by stem cell-derived exosomes encapsulated in silk fibroin hydrogel prevents aging-induced vascular dysfunction in mouse hindlimb. Mater. Sci. Eng. C Mater. Biol. Appl. 2019, 99, 322–332. [Google Scholar] [CrossRef] [PubMed]
- Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341–345. [Google Scholar] [CrossRef] [PubMed]
- Ju, Z.; Ma, J.; Wang, C.; Yu, J.; Qiao, Y.; Hei, F. Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells. Inflammation 2017, 40, 486–496. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, F.J. Biomaterials & scaffolds for tissue engineering. Mater. Today 2011, 14, 88–95. [Google Scholar]
- Xie, H.; Wang, Z.; Zhang, L.; Lei, Q.; Zhao, A.; Wang, H.; Li, Q.; Cao, Y.; Jie Zhang, W.; Chen, Z. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities. Sci. Rep. 2017, 7, 45622. [Google Scholar] [CrossRef]
- Li, W.; Liu, Y.; Zhang, P.; Tang, Y.; Zhou, M.; Jiang, W.; Zhang, X.; Wu, G.; Zhou, Y. Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration. ACS Appl. Mater. Interfaces 2018, 10, 5240–5254. [Google Scholar] [CrossRef] [PubMed]
- Shi, Q.; Qian, Z.; Liu, D.; Sun, J.; Wang, X.; Liu, H.; Xu, J.; Guo, X. GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model. Front. Physiol. 2017, 8, 904. [Google Scholar] [CrossRef] [PubMed]
- Liu, B.; Lee, B.W.; Nakanishi, K.; Villasante, A.; Williamson, R.; Metz, J.; Kim, J.; Kanai, M.; Bi, L.; Brown, K.; et al. Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells. Nat. Biomed. Eng. 2018, 2, 293–303. [Google Scholar] [CrossRef]
- Xin, H.; Katakowski, M.; Wang, F.; Qian, J.Y.; Liu, X.S.; Ali, M.M.; Buller, B.; Zhang, Z.G.; Chopp, M. MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats. Stroke 2017, 48, 747–753. [Google Scholar] [CrossRef]
- Gimona, M.; Pachler, K.; Laner-Plamberger, S.; Schallmoser, K.; Rohde, E. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use. Int. J. Mol. Sci. 2017, 18, 1190. [Google Scholar] [CrossRef]
Property | Exosomes | Membrane Vesicles | Apoptotic Bodies |
---|---|---|---|
Size | 30–120 nm | 100–1000 nm | 50–4000 nm |
Morphology | Homogenous cup-shape | Heterogeneous irregular | Heterogeneous irregular |
Buoyant density | 1.13–1.19 g/cm3 | Not well defined | 1.16–1.28 g/cm3 |
Origin | Endosomal | Plasma membrane | Apoptotic cells |
Proteins | CD63, CD81, CD9, annexins, heat-shock proteins, Alix, Tsg101, clathrin, caveolins, integrins, TfRs | Integrins, flotillins, selectins, CD40, metalloproteinases | Histones |
Lipids | Lysobisphosphatidic acid, cholesterol, ceramide, sphingomyelin and low concentration of phosphatidylserine | High amount of cholesterol, sphingomyelin, ceramide, high concentration of phosphatidylserine | High concentration of phosphatidylserine |
Nucleic Acids | mRNA, lncRNAs and miRNAs | mRNA, lncRNAs and miRNAs | mRNA, miRNA, fragments of DNA |
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Barreca, M.M.; Cancemi, P.; Geraci, F. Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine? Cells 2020, 9, 1163. https://doi.org/10.3390/cells9051163
Barreca MM, Cancemi P, Geraci F. Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine? Cells. 2020; 9(5):1163. https://doi.org/10.3390/cells9051163
Chicago/Turabian StyleBarreca, Maria Magdalena, Patrizia Cancemi, and Fabiana Geraci. 2020. "Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine?" Cells 9, no. 5: 1163. https://doi.org/10.3390/cells9051163
APA StyleBarreca, M. M., Cancemi, P., & Geraci, F. (2020). Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine? Cells, 9(5), 1163. https://doi.org/10.3390/cells9051163