Concise review: Extracellular vesicles from mesenchymal stem cells as cellular therapy
DOI:
https://doi.org/10.15419/bmrat.v4i08.287Keywords:
Extracellular vesicles, stem cells, Regenerative medicineAbstract
Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are microvesicles produced from cells throughout their life. From research over recent years, there has been greater understanding about EVs, including their physiological characteristics and the role they play in cell targets. Indeed, EVs carry information (in the form of RNA, DNA and protein) to cell targets. Some of their main biological properties include angiogenesis and immune-modulation. Therefore, these properties can be exploited to treat various diseases, including bone disorders, spinal cord injury and diabetes mellitus. Recently, new methods have been developed to isolate and enrich EVs with high performance and low-toxicity. Thus, EVs have emerged as the new generation of stem cell therapy. This concise review aims to highlight some recent achievements of EVs in preclinical and clinical applications.
References
<ol>
<li class="show">Abdi, R., Fiorina, P., Adra, C. N., Atkinson, M., & Sayegh, M. H. (2008). Immunomodulation by mesenchymal stem cells: A potential therapeutic strategy for type 1 diabetes. Diabetes, 57(7), 1759–1767. <a href="https://doi.org/10.2337/db08-0180">https://doi.org/10.2337/db08-0180</a></li>
<li class="show">Baglio, S. R., Pegtel, D. M., & Baldini, N. (2012). Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Frontiers in Physiology, 3, 359. <a href="https://doi.org/10.3389/fphys.2012.00359">https://doi.org/10.3389/fphys.2012.00359</a></li>
<li class="show">Biancone, L., Bruno, S., Deregibus, M. C., Tetta, C., & Camussi, G. (2012). Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrology, Dialysis, Transplantation, 27(8), 3037–3042. <a href="https://doi.org/10.1093/ndt/gfs168">https://doi.org/10.1093/ndt/gfs168</a></li>
<li class="show">Blazquez, R., Sanchez-Margallo, F. M., de la Rosa, O., Dalemans, W., Álvarez, V., Tarazona, R., & Casado, J. G. (2014). Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Frontiers in Immunology, 5, 556. <a href="https://doi.org/10.3389/fimmu.2014.00556">https://doi.org/10.3389/fimmu.2014.00556</a></li>
<li class="show">Bongso, A., & Lee, E. H. (2005). Stem cells: from bench to bedside. World Scientific. <a href="https://doi.org/10.1142/5729">https://doi.org/10.1142/5729</a></li>
<li class="show">Boomsma, R. A., & Geenen, D. L. (2012). Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis. PLoS One, 7(4), e35685. <a href="https://doi.org/10.1371/journal.pone.0035685">https://doi.org/10.1371/journal.pone.0035685</a></li>
<li class="show">Börger, V., Bremer, M., Ferrer-Tur, R., Gockeln, L., Stambouli, O., Becic, A., & Giebel, B. (2017). Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. International Journal of Molecular Sciences, 18(7), 18.</li>
<li class="show">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 Transplantation, 22(2), 369–379.</li>
<li class="show">Camussi, G., Deregibus, M.-C., Bruno, S., Grange, C., Fonsato, V., & Tetta, C. (2011). Exosome/microvesicle-mediated epigenetic reprogramming of cells. American Journal of Cancer Research, 1(1), 98–110.</li>
<li class="show">Camussi, G., Deregibus, M. C., Bruno, S., Cantaluppi, V., & Biancone, L. (2010). Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney International, 78(9), 838–848. <a href="https://doi.org/10.1038/ki.2010.278">https://doi.org/10.1038/ki.2010.278</a></li>
<li class="show">Chase, L. G., & Vemuri, M. C. (2012). Mesenchymal stem cell therapy. Springer Science & Business Media.<br>Chen, W., Huang, Y., Han, J., Yu, L., Li, Y., Lu, Z., . . . Xiao, Y. (2016). Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunologic Research, 64(4), 831–840. <a href="https://doi.org/10.1007/s12026-016-8798-6">https://doi.org/10.1007/s12026-016-8798-6</a></li>
<li class="show">Collino, F., Deregibus, M. C., Bruno, S., Sterpone, L., Aghemo, G., Viltono, L., . . . Camussi, G. (2010). Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One, 5(7), e11803. <a href="https://doi.org/10.1371/journal.pone.0011803">https://doi.org/10.1371/journal.pone.0011803</a></li>
<li class="show">Conforti, A., Scarsella, M., Starc, N., Giorda, E., Biagini, S., Proia, A., . . . Bernardo, M. E. (2014). Microvescicles derived from mesenchymal stromal cells are not as effective as their cellular counterpart in the ability to modulate immune responses in vitro. Stem Cells and Development, 23(21), 2591–2599. <a href="https://doi.org/10.1089/scd.2014.0091">https://doi.org/10.1089/scd.2014.0091</a></li>
<li class="show">Crescitelli, R., Lässer, C., Szabó, T. G., Kittel, A., Eldh, M., Dianzani, I., . . . Lötvall, J. (2013). Distinct RNA profiles in subpopulations of extracellular vesicles: Apoptotic bodies, microvesicles and exosomes. Journal of Extracellular Vesicles, 2(1), 20677. <a href="https://doi.org/10.3402/jev.v2i0.20677">https://doi.org/10.3402/jev.v2i0.20677</a></li>
<li class="show">Meirelles, L. S., Fontes, A. M., Covas, D. T., & Caplan, A. I. (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine & Growth Factor Reviews, 20(5-6), 419–427. <a href="https://doi.org/10.1016/j.cytogfr.2009.10.002">https://doi.org/10.1016/j.cytogfr.2009.10.002</a></li>
<li class="show">De Luca, L., Trino, S., Laurenzana, I., Simeon, V., Calice, G., Raimondo, S., . . . Musto, P. (2016). 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, 7(6), 6676–6692. <a href="https://doi.org/10.18632/oncotarget.6791">https://doi.org/10.18632/oncotarget.6791</a></li>
<li class="show">Doeppner, T. R., Herz, J., Görgens, A., Schlechter, J., Ludwig, A.-K., Radtke, S., . . . Hermann, D. M. (2015). Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Translational Medicine, 4(10), 1131–1143. <a href="https://doi.org/10.5966/sctm.2015-0078">https://doi.org/10.5966/sctm.2015-0078</a></li>
<li class="show">Eirin, A., Riester, S. M., Zhu, X.-Y., Tang, H., Evans, J. M., O’Brien, D., . . . Lerman, L. O. (2014). MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells. Gene, 551(1), 55–64. <a href="https://doi.org/10.1016/j.gene.2014.08.041">https://doi.org/10.1016/j.gene.2014.08.041</a></li>
<li class="show">Fafián-Labora, J., Lesende-Rodriguez, I., Fernández-Pernas, P., Sangiao-Alvarellos, S., Monserrat, L., Arntz, O. J., . . . Arufe, M. C. (2017). Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles. Scientific Reports, 7, 43923. <a href="https://doi.org/10.1038/srep43923">https://doi.org/10.1038/srep43923</a></li>
<li class="show">Ginn, S. L., Alexander, I. E., Edelstein, M. L., Abedi, M. R., & Wixon, J. (2013). Gene therapy clinical trials worldwide to 2012 - an update. The Journal of Gene Medicine, 15(2), 65–77.<a href=" https://doi.org/10.1002/jgm.269"> https://doi.org/10.1002/jgm.269</a>8</li>
<li class="show">Han, D., Wu, C., Xiong, Q., Zhou, L., & Tian, Y. (2015). Anti-inflammatory mechanism of bone marrow mesenchymal stem cell transplantation in rat model of spinal cord injury. Cell Biochemistry and Biophysics, 71(3), 1341–1347. <a href="https://doi.org/10.1007/s12013-014-0354-1">https://doi.org/10.1007/s12013-014-0354-1</a></li>
<li class="show">Hu, L., Wang, J., Zhou, X., Xiong, Z., Zhao, J., Yu, R., . . . Chen, L. (2016). Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Scientific Reports, 6(1), 32993. <a href="https://doi.org/10.1038/srep32993">https://doi.org/10.1038/srep32993</a></li>
<li class="show">Kastelowitz, N., & Yin, H. (2014). Exosomes and microvesicles: Identification and targeting by particle size and lipid chemical probes. ChemBioChem, 15(7), 923–928. <a href="https://doi.org/10.1002/cbic.201400043">https://doi.org/10.1002/cbic.201400043</a></li>
<li class="show">Kilroy, G. E., Foster, S. J., Wu, X., Ruiz, J., Sherwood, S., Heifetz, A., . . . Gimble, J. M. (2007). Cytokine profile of human adipose-derived stem cells: Expression of angiogenic, hematopoietic, and pro-inflammatory factors. Journal of Cellular Physiology, 212(3), 702–709. <a href="https://doi.org/10.1002/jcp.21068">https://doi.org/10.1002/jcp.21068</a></li>
<li class="show">Kordelas, L., Rebmann, V., Ludwig, A. K., Radtke, S., Ruesing, J., Doeppner, T. R., . . . Giebel, B. (2014). MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease. Leukemia, 28(4), 970–973.</li>
<li class="show">Kumar, L., Verma, S., Vaidya, B., & Gupta, V. (2015). Exosomes: Natural carriers for siRNA delivery. Current Pharmaceutical Design, 21(31), 4556–4565. <a href="https://doi.org/10.2174/138161282131151013190112">https://doi.org/10.2174/138161282131151013190112</a><br>Lai, R.C., Yeo, R.W.Y., and Lim, S.K. (2015). Mesenchymal stem cell exosomes. Paper presented at: Seminars in Cell & Developmental Biology (Elsevier). <a href="https://doi.org/10.1016/j.semcdb.2015.03.001">https://doi.org/10.1016/j.semcdb.2015.03.001</a></li>
<li class="show">Lespagnol, A., Duflaut, D., Beekman, C., Blanc, L., Fiucci, G., Marine, J. C., . . . Telerman, A. (2008). Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death and Differentiation, 15(11), 1723–1733. <a href="https://doi.org/10.1038/cdd.2008.104">https://doi.org/10.1038/cdd.2008.104</a></li>
<li class="show">Liu, X., Li, Q., Niu, X., Hu, B., Chen, S., Song, W., . . . Wang, Y. (2017). Exosomes Secreted from Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Prevent Osteonecrosis of the Femoral Head by Promoting Angiogenesis. International Journal of Biological Sciences, 13(2), 232–244. <a href="https://doi.org/10.7150/ijbs.16951">https://doi.org/10.7150/ijbs.16951</a></li>
<li class="show">Livingston, M. J., & Wei, Q. (2016). MicroRNAs in extracellular vesicles protect kidney from ischemic injury: From endothelial to tubular epithelial. Kidney International, 90(6), 1150–1152. <a href="https://doi.org/10.1016/j.kint.2016.08.032">https://doi.org/10.1016/j.kint.2016.08.032</a></li>
<li class="show">Lo Sicco, C., Reverberi, D., Balbi, C., Ulivi, V., Principi, E., Pascucci, L., . . . Tasso, R. (2017). Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization. Stem Cells Translational Medicine, 6(3), 1018–1028. <a href="https://doi.org/10.1002/sctm.16-0363">https://doi.org/10.1002/sctm.16-0363</a></li>
<li class="show">Meehan, B., Rak, J., & Di Vizio, D. (2016). Oncosomes - large and small: What are they, where they came from? Journal of Extracellular Vesicles, 5(1), 33109. <a href="https://doi.org/10.3402/jev.v5.33109">https://doi.org/10.3402/jev.v5.33109</a></li>
<li class="show">Mokarizadeh, A., Delirezh, N., Morshedi, A., Mosayebi, G., Farshid, A.-A., & Mardani, K. (2012). Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling. Immunology Letters, 147(1-2), 47–54. <a href="https://doi.org/10.1016/j.imlet.2012.06.001">https://doi.org/10.1016/j.imlet.2012.06.001</a></li>
<li class="show">Nawaz, M., Fatima, F., Vallabhaneni, K. C., Penfornis, P., Valadi, H., Ekström, K., . . . Camussi, G. (2016). Extracellular Vesicles: Evolving Factors in Stem Cell Biology. Stem Cells International, 2016, 1073140. <a href="https://doi.org/10.1155/2016/1073140">https://doi.org/10.1155/2016/1073140</a></li>
<li class="show">Ostrowski, M., Carmo, N.B., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C.F., Schauer, K., Hume, A.N., Freitas, R.P., et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature cell biology 12, 19-30; sup pp 11-13.</li>
<li class="show">Pols, M. S., & Klumperman, J. (2009). Trafficking and function of the tetraspanin CD63. Experimental Cell Research, 315(9), 1584–1592. <a href="https://doi.org/10.1016/j.yexcr.2008.09.020">https://doi.org/10.1016/j.yexcr.2008.09.020</a></li>
<li class="show">Prockop, D. J., & Oh, J. Y. (2012). Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Molecular Therapy, 20(1), 14–20. <a href="https://doi.org/10.1038/mt.2011.211">https://doi.org/10.1038/mt.2011.211</a></li>
<li class="show">Qin, Y., Wang, L., Gao, Z., Chen, G., & Zhang, C. (2016). Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Scientific Reports, 6(1), 21961. <a href="https://doi.org/10.1038/srep21961">https://doi.org/10.1038/srep21961</a></li>
<li class="show">Rak, J. (2013). Extracellular vesicles - biomarkers and effectors of the cellular interactome in cancer. Frontiers in Pharmacology, 4, 21.<a href=" https://doi.org/10.3389/fphar.2013.00021"> https://doi.org/10.3389/fphar.2013.00021</a></li>
<li class="show">Rani, S., Ryan, A. E., Griffin, M. D., & Ritter, T. (2015). Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Molecular Therapy, 23(5), 812–823. <a href="https://doi.org/10.1038/mt.2015.44">https://doi.org/10.1038/mt.2015.44</a></li>
<li class="show">Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: Exosomes, microvesicles, and friends. The Journal of Cell Biology, 200(4), 373–383. <a href="https://doi.org/10.1083/jcb.201211138">https://doi.org/10.1083/jcb.201211138</a></li>
<li class="show">de Rivero Vaccari, J. P., Brand, F., III, Adamczak, S., Lee, S. W., Perez-Barcena, J., Wang, M. Y., . . . Keane, R. W. (2016). Exosome-mediated inflammasome signaling after central nervous system injury. Journal of Neurochemistry, 136(Suppl 1), 39–48. <a href="https://doi.org/10.1111/jnc.13036">https://doi.org/10.1111/jnc.13036</a></li>
<li class="show">Shigemoto-Kuroda, T., Oh, J. Y., Kim, D. K., Jeong, H. J., Park, S. Y., Lee, H. J., . . . Lee, R. H. (2017). MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis. Stem Cell Reports, 8(5), 1214–1225. <a href="https://doi.org/10.1016/j.stemcr.2017.04.008">https://doi.org/10.1016/j.stemcr.2017.04.008</a></li>
<li class="show">Squillaro, T., Peluso, G., & Galderisi, U. (2016). Clinical trials with mesenchymal stem cells: An update. Cell Transplantation, 25(5), 829–848. <a href="https://doi.org/10.3727/096368915X689622">https://doi.org/10.3727/096368915X689622</a></li>
<li class="show">Stoorvogel, W., Kleijmeer, M. J., Geuze, H. J., & Raposo, G. (2002). The biogenesis and functions of exosomes. Traffic (Copenhagen, Denmark), 3(5), 321–330. <a href="https://doi.org/10.1034/j.1600-0854.2002.30502.x">https://doi.org/10.1034/j.1600-0854.2002.30502.x</a></li>
<li class="show">Teixeira, F. G., Carvalho, M. M., Neves-Carvalho, A., Panchalingam, K. M., Behie, L. A., Pinto, L., . . . Salgado, A. J. (2015). Secretome of mesenchymal progenitors from the umbilical cord acts as modulator of neural/glial proliferation and differentiation. Stem Cell Reviews and Reports, 11(2), 288–297. <a href="https://doi.org/10.1007/s12015-014-9576-2">https://doi.org/10.1007/s12015-014-9576-2</a></li>
<li class="show">Tomasoni, S., Longaretti, L., Rota, C., Morigi, M., Conti, S., Gotti, E., . . . Benigni, A. (2013). Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells. Stem Cells and Development, 22(5), 772–780. <a href="https://doi.org/10.1089/scd.2012.0266">https://doi.org/10.1089/scd.2012.0266</a></li>
<li class="show">Vallabhaneni, K. C., Penfornis, P., Dhule, S., Guillonneau, F., Adams, K. V., Mo, Y. Y., . . . Pochampally, R. (2015). Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites. Oncotarget, 6(7), 4953–4967. <a href="https://doi.org/10.18632/oncotarget.3211">https://doi.org/10.18632/oncotarget.3211</a></li>
<li class="show">Van Pham, P. (2016). Clinical application of stem cells: An update 2015. Biomedical Research and Therapy, 3(2), 483–489. <a href="https://doi.org/10.7603/s40730-016-0005-9">https://doi.org/10.7603/s40730-016-0005-9</a></li>
<li class="show">Wang, J., Cen, P., Chen, J., Fan, L., Li, J., Cao, H., & Li, L. (2017). Role of mesenchymal stem cells, their derived factors, and extracellular vesicles in liver failure. Stem Cell Research & Therapy, 8(1), 137. <a href="https://doi.org/10.1186/s13287-017-0576-4">https://doi.org/10.1186/s13287-017-0576-4</a></li>
<li class="show">Wang, L., Gu, Z., Zhao, X., Yang, N., Wang, F., Deng, A., . . . Gao, C. (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 and Development, 25(24), 1874–1883. <a href="https://doi.org/10.1089/scd.2016.0107">https://doi.org/10.1089/scd.2016.0107</a></li>
<li class="show">Yañez, R., Lamana, M. L., García-Castro, J., Colmenero, I., Ramírez, M., & Bueren, J. A. (2006). Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells (Dayton, Ohio), 24(11), 2582–2591. <a href="https://doi.org/10.1089/scd.2016.0107">https://doi.org/10.1634/stemcells.2006-0228</a></li>
<li class="show">Yáñez-Mó, M., Siljander, P. R., Andreu, Z., Zavec, A. B., Borràs, F. E., Buzas, E. I., . . . De Wever, O. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1), 27066. <a href="https://doi.org/10.3402/jev.v4.27066">https://doi.org/10.3402/jev.v4.27066</a></li>
<li class="show">Yu, B., Zhang, X., & Li, X. (2014). Exosomes derived from mesenchymal stem cells. International Journal of Molecular Sciences, 15(3), 4142–4157. <a href="https://doi.org/10.3390/ijms15034142">https://doi.org/10.3390/ijms15034142</a></li>
<li class="show">Yuan, Z., Kolluri, K. K., Gowers, K. H. C., & Janes, S. M. (2017). TRAIL delivery by MSC-derived extracellular vesicles is an effective anticancer therapy. Journal of Extracellular Vesicles, 6(1), 1265291. <a href="https://doi.org/10.1080/20013078.2017.1265291">https://doi.org/10.1080/20013078.2017.1265291</a></li>
<li class="show">Zhang, B., Wang, M., Gong, A., Zhang, X., Wu, X., Zhu, Y., . . . Xu, W. (2015a). HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells (Dayton, Ohio), 33(7), 2158–2168. <a href="https://doi.org/10.1002/stem.1771">https://doi.org/10.1002/stem.1771</a></li>
<li class="show">Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., . . . Xu, W. (2015b). Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Translational Medicine, 4(5), 513–522.<a href=" https://doi.org/10.5966/sctm.2014-0267"> https://doi.org/10.5966/sctm.2014-0267</a></li>
<li class="show">Zhang, B., Yin, Y., Lai, R. C., Tan, S. S., Choo, A. B., & Lim, S. K. (2014). Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells and Development, 23(11), 1233–1244. <a href="https://doi.org/10.1089/scd.2013.0479">https://doi.org/10.1089/scd.2013.0479</a></li>
<li class="show">Zhang, S., Chu, W. C., Lai, R. C., Lim, S. K., Hui, J. H., & Toh, W. S. (2016). Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis and Cartilage, 24(12), 2135–2140. <a href="https://doi.org/10.1016/j.joca.2016.06.022">https://doi.org/10.1016/j.joca.2016.06.022</a></li>
</ol>
<li class="show">Abdi, R., Fiorina, P., Adra, C. N., Atkinson, M., & Sayegh, M. H. (2008). Immunomodulation by mesenchymal stem cells: A potential therapeutic strategy for type 1 diabetes. Diabetes, 57(7), 1759–1767. <a href="https://doi.org/10.2337/db08-0180">https://doi.org/10.2337/db08-0180</a></li>
<li class="show">Baglio, S. R., Pegtel, D. M., & Baldini, N. (2012). Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Frontiers in Physiology, 3, 359. <a href="https://doi.org/10.3389/fphys.2012.00359">https://doi.org/10.3389/fphys.2012.00359</a></li>
<li class="show">Biancone, L., Bruno, S., Deregibus, M. C., Tetta, C., & Camussi, G. (2012). Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrology, Dialysis, Transplantation, 27(8), 3037–3042. <a href="https://doi.org/10.1093/ndt/gfs168">https://doi.org/10.1093/ndt/gfs168</a></li>
<li class="show">Blazquez, R., Sanchez-Margallo, F. M., de la Rosa, O., Dalemans, W., Álvarez, V., Tarazona, R., & Casado, J. G. (2014). Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Frontiers in Immunology, 5, 556. <a href="https://doi.org/10.3389/fimmu.2014.00556">https://doi.org/10.3389/fimmu.2014.00556</a></li>
<li class="show">Bongso, A., & Lee, E. H. (2005). Stem cells: from bench to bedside. World Scientific. <a href="https://doi.org/10.1142/5729">https://doi.org/10.1142/5729</a></li>
<li class="show">Boomsma, R. A., & Geenen, D. L. (2012). Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis. PLoS One, 7(4), e35685. <a href="https://doi.org/10.1371/journal.pone.0035685">https://doi.org/10.1371/journal.pone.0035685</a></li>
<li class="show">Börger, V., Bremer, M., Ferrer-Tur, R., Gockeln, L., Stambouli, O., Becic, A., & Giebel, B. (2017). Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. International Journal of Molecular Sciences, 18(7), 18.</li>
<li class="show">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 Transplantation, 22(2), 369–379.</li>
<li class="show">Camussi, G., Deregibus, M.-C., Bruno, S., Grange, C., Fonsato, V., & Tetta, C. (2011). Exosome/microvesicle-mediated epigenetic reprogramming of cells. American Journal of Cancer Research, 1(1), 98–110.</li>
<li class="show">Camussi, G., Deregibus, M. C., Bruno, S., Cantaluppi, V., & Biancone, L. (2010). Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney International, 78(9), 838–848. <a href="https://doi.org/10.1038/ki.2010.278">https://doi.org/10.1038/ki.2010.278</a></li>
<li class="show">Chase, L. G., & Vemuri, M. C. (2012). Mesenchymal stem cell therapy. Springer Science & Business Media.<br>Chen, W., Huang, Y., Han, J., Yu, L., Li, Y., Lu, Z., . . . Xiao, Y. (2016). Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunologic Research, 64(4), 831–840. <a href="https://doi.org/10.1007/s12026-016-8798-6">https://doi.org/10.1007/s12026-016-8798-6</a></li>
<li class="show">Collino, F., Deregibus, M. C., Bruno, S., Sterpone, L., Aghemo, G., Viltono, L., . . . Camussi, G. (2010). Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One, 5(7), e11803. <a href="https://doi.org/10.1371/journal.pone.0011803">https://doi.org/10.1371/journal.pone.0011803</a></li>
<li class="show">Conforti, A., Scarsella, M., Starc, N., Giorda, E., Biagini, S., Proia, A., . . . Bernardo, M. E. (2014). Microvescicles derived from mesenchymal stromal cells are not as effective as their cellular counterpart in the ability to modulate immune responses in vitro. Stem Cells and Development, 23(21), 2591–2599. <a href="https://doi.org/10.1089/scd.2014.0091">https://doi.org/10.1089/scd.2014.0091</a></li>
<li class="show">Crescitelli, R., Lässer, C., Szabó, T. G., Kittel, A., Eldh, M., Dianzani, I., . . . Lötvall, J. (2013). Distinct RNA profiles in subpopulations of extracellular vesicles: Apoptotic bodies, microvesicles and exosomes. Journal of Extracellular Vesicles, 2(1), 20677. <a href="https://doi.org/10.3402/jev.v2i0.20677">https://doi.org/10.3402/jev.v2i0.20677</a></li>
<li class="show">Meirelles, L. S., Fontes, A. M., Covas, D. T., & Caplan, A. I. (2009). Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine & Growth Factor Reviews, 20(5-6), 419–427. <a href="https://doi.org/10.1016/j.cytogfr.2009.10.002">https://doi.org/10.1016/j.cytogfr.2009.10.002</a></li>
<li class="show">De Luca, L., Trino, S., Laurenzana, I., Simeon, V., Calice, G., Raimondo, S., . . . Musto, P. (2016). 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, 7(6), 6676–6692. <a href="https://doi.org/10.18632/oncotarget.6791">https://doi.org/10.18632/oncotarget.6791</a></li>
<li class="show">Doeppner, T. R., Herz, J., Görgens, A., Schlechter, J., Ludwig, A.-K., Radtke, S., . . . Hermann, D. M. (2015). Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Translational Medicine, 4(10), 1131–1143. <a href="https://doi.org/10.5966/sctm.2015-0078">https://doi.org/10.5966/sctm.2015-0078</a></li>
<li class="show">Eirin, A., Riester, S. M., Zhu, X.-Y., Tang, H., Evans, J. M., O’Brien, D., . . . Lerman, L. O. (2014). MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells. Gene, 551(1), 55–64. <a href="https://doi.org/10.1016/j.gene.2014.08.041">https://doi.org/10.1016/j.gene.2014.08.041</a></li>
<li class="show">Fafián-Labora, J., Lesende-Rodriguez, I., Fernández-Pernas, P., Sangiao-Alvarellos, S., Monserrat, L., Arntz, O. J., . . . Arufe, M. C. (2017). Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles. Scientific Reports, 7, 43923. <a href="https://doi.org/10.1038/srep43923">https://doi.org/10.1038/srep43923</a></li>
<li class="show">Ginn, S. L., Alexander, I. E., Edelstein, M. L., Abedi, M. R., & Wixon, J. (2013). Gene therapy clinical trials worldwide to 2012 - an update. The Journal of Gene Medicine, 15(2), 65–77.<a href=" https://doi.org/10.1002/jgm.269"> https://doi.org/10.1002/jgm.269</a>8</li>
<li class="show">Han, D., Wu, C., Xiong, Q., Zhou, L., & Tian, Y. (2015). Anti-inflammatory mechanism of bone marrow mesenchymal stem cell transplantation in rat model of spinal cord injury. Cell Biochemistry and Biophysics, 71(3), 1341–1347. <a href="https://doi.org/10.1007/s12013-014-0354-1">https://doi.org/10.1007/s12013-014-0354-1</a></li>
<li class="show">Hu, L., Wang, J., Zhou, X., Xiong, Z., Zhao, J., Yu, R., . . . Chen, L. (2016). Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Scientific Reports, 6(1), 32993. <a href="https://doi.org/10.1038/srep32993">https://doi.org/10.1038/srep32993</a></li>
<li class="show">Kastelowitz, N., & Yin, H. (2014). Exosomes and microvesicles: Identification and targeting by particle size and lipid chemical probes. ChemBioChem, 15(7), 923–928. <a href="https://doi.org/10.1002/cbic.201400043">https://doi.org/10.1002/cbic.201400043</a></li>
<li class="show">Kilroy, G. E., Foster, S. J., Wu, X., Ruiz, J., Sherwood, S., Heifetz, A., . . . Gimble, J. M. (2007). Cytokine profile of human adipose-derived stem cells: Expression of angiogenic, hematopoietic, and pro-inflammatory factors. Journal of Cellular Physiology, 212(3), 702–709. <a href="https://doi.org/10.1002/jcp.21068">https://doi.org/10.1002/jcp.21068</a></li>
<li class="show">Kordelas, L., Rebmann, V., Ludwig, A. K., Radtke, S., Ruesing, J., Doeppner, T. R., . . . Giebel, B. (2014). MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease. Leukemia, 28(4), 970–973.</li>
<li class="show">Kumar, L., Verma, S., Vaidya, B., & Gupta, V. (2015). Exosomes: Natural carriers for siRNA delivery. Current Pharmaceutical Design, 21(31), 4556–4565. <a href="https://doi.org/10.2174/138161282131151013190112">https://doi.org/10.2174/138161282131151013190112</a><br>Lai, R.C., Yeo, R.W.Y., and Lim, S.K. (2015). Mesenchymal stem cell exosomes. Paper presented at: Seminars in Cell & Developmental Biology (Elsevier). <a href="https://doi.org/10.1016/j.semcdb.2015.03.001">https://doi.org/10.1016/j.semcdb.2015.03.001</a></li>
<li class="show">Lespagnol, A., Duflaut, D., Beekman, C., Blanc, L., Fiucci, G., Marine, J. C., . . . Telerman, A. (2008). Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death and Differentiation, 15(11), 1723–1733. <a href="https://doi.org/10.1038/cdd.2008.104">https://doi.org/10.1038/cdd.2008.104</a></li>
<li class="show">Liu, X., Li, Q., Niu, X., Hu, B., Chen, S., Song, W., . . . Wang, Y. (2017). Exosomes Secreted from Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Prevent Osteonecrosis of the Femoral Head by Promoting Angiogenesis. International Journal of Biological Sciences, 13(2), 232–244. <a href="https://doi.org/10.7150/ijbs.16951">https://doi.org/10.7150/ijbs.16951</a></li>
<li class="show">Livingston, M. J., & Wei, Q. (2016). MicroRNAs in extracellular vesicles protect kidney from ischemic injury: From endothelial to tubular epithelial. Kidney International, 90(6), 1150–1152. <a href="https://doi.org/10.1016/j.kint.2016.08.032">https://doi.org/10.1016/j.kint.2016.08.032</a></li>
<li class="show">Lo Sicco, C., Reverberi, D., Balbi, C., Ulivi, V., Principi, E., Pascucci, L., . . . Tasso, R. (2017). Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization. Stem Cells Translational Medicine, 6(3), 1018–1028. <a href="https://doi.org/10.1002/sctm.16-0363">https://doi.org/10.1002/sctm.16-0363</a></li>
<li class="show">Meehan, B., Rak, J., & Di Vizio, D. (2016). Oncosomes - large and small: What are they, where they came from? Journal of Extracellular Vesicles, 5(1), 33109. <a href="https://doi.org/10.3402/jev.v5.33109">https://doi.org/10.3402/jev.v5.33109</a></li>
<li class="show">Mokarizadeh, A., Delirezh, N., Morshedi, A., Mosayebi, G., Farshid, A.-A., & Mardani, K. (2012). Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling. Immunology Letters, 147(1-2), 47–54. <a href="https://doi.org/10.1016/j.imlet.2012.06.001">https://doi.org/10.1016/j.imlet.2012.06.001</a></li>
<li class="show">Nawaz, M., Fatima, F., Vallabhaneni, K. C., Penfornis, P., Valadi, H., Ekström, K., . . . Camussi, G. (2016). Extracellular Vesicles: Evolving Factors in Stem Cell Biology. Stem Cells International, 2016, 1073140. <a href="https://doi.org/10.1155/2016/1073140">https://doi.org/10.1155/2016/1073140</a></li>
<li class="show">Ostrowski, M., Carmo, N.B., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C.F., Schauer, K., Hume, A.N., Freitas, R.P., et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature cell biology 12, 19-30; sup pp 11-13.</li>
<li class="show">Pols, M. S., & Klumperman, J. (2009). Trafficking and function of the tetraspanin CD63. Experimental Cell Research, 315(9), 1584–1592. <a href="https://doi.org/10.1016/j.yexcr.2008.09.020">https://doi.org/10.1016/j.yexcr.2008.09.020</a></li>
<li class="show">Prockop, D. J., & Oh, J. Y. (2012). Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Molecular Therapy, 20(1), 14–20. <a href="https://doi.org/10.1038/mt.2011.211">https://doi.org/10.1038/mt.2011.211</a></li>
<li class="show">Qin, Y., Wang, L., Gao, Z., Chen, G., & Zhang, C. (2016). Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Scientific Reports, 6(1), 21961. <a href="https://doi.org/10.1038/srep21961">https://doi.org/10.1038/srep21961</a></li>
<li class="show">Rak, J. (2013). Extracellular vesicles - biomarkers and effectors of the cellular interactome in cancer. Frontiers in Pharmacology, 4, 21.<a href=" https://doi.org/10.3389/fphar.2013.00021"> https://doi.org/10.3389/fphar.2013.00021</a></li>
<li class="show">Rani, S., Ryan, A. E., Griffin, M. D., & Ritter, T. (2015). Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Molecular Therapy, 23(5), 812–823. <a href="https://doi.org/10.1038/mt.2015.44">https://doi.org/10.1038/mt.2015.44</a></li>
<li class="show">Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: Exosomes, microvesicles, and friends. The Journal of Cell Biology, 200(4), 373–383. <a href="https://doi.org/10.1083/jcb.201211138">https://doi.org/10.1083/jcb.201211138</a></li>
<li class="show">de Rivero Vaccari, J. P., Brand, F., III, Adamczak, S., Lee, S. W., Perez-Barcena, J., Wang, M. Y., . . . Keane, R. W. (2016). Exosome-mediated inflammasome signaling after central nervous system injury. Journal of Neurochemistry, 136(Suppl 1), 39–48. <a href="https://doi.org/10.1111/jnc.13036">https://doi.org/10.1111/jnc.13036</a></li>
<li class="show">Shigemoto-Kuroda, T., Oh, J. Y., Kim, D. K., Jeong, H. J., Park, S. Y., Lee, H. J., . . . Lee, R. H. (2017). MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis. Stem Cell Reports, 8(5), 1214–1225. <a href="https://doi.org/10.1016/j.stemcr.2017.04.008">https://doi.org/10.1016/j.stemcr.2017.04.008</a></li>
<li class="show">Squillaro, T., Peluso, G., & Galderisi, U. (2016). Clinical trials with mesenchymal stem cells: An update. Cell Transplantation, 25(5), 829–848. <a href="https://doi.org/10.3727/096368915X689622">https://doi.org/10.3727/096368915X689622</a></li>
<li class="show">Stoorvogel, W., Kleijmeer, M. J., Geuze, H. J., & Raposo, G. (2002). The biogenesis and functions of exosomes. Traffic (Copenhagen, Denmark), 3(5), 321–330. <a href="https://doi.org/10.1034/j.1600-0854.2002.30502.x">https://doi.org/10.1034/j.1600-0854.2002.30502.x</a></li>
<li class="show">Teixeira, F. G., Carvalho, M. M., Neves-Carvalho, A., Panchalingam, K. M., Behie, L. A., Pinto, L., . . . Salgado, A. J. (2015). Secretome of mesenchymal progenitors from the umbilical cord acts as modulator of neural/glial proliferation and differentiation. Stem Cell Reviews and Reports, 11(2), 288–297. <a href="https://doi.org/10.1007/s12015-014-9576-2">https://doi.org/10.1007/s12015-014-9576-2</a></li>
<li class="show">Tomasoni, S., Longaretti, L., Rota, C., Morigi, M., Conti, S., Gotti, E., . . . Benigni, A. (2013). Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells. Stem Cells and Development, 22(5), 772–780. <a href="https://doi.org/10.1089/scd.2012.0266">https://doi.org/10.1089/scd.2012.0266</a></li>
<li class="show">Vallabhaneni, K. C., Penfornis, P., Dhule, S., Guillonneau, F., Adams, K. V., Mo, Y. Y., . . . Pochampally, R. (2015). Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites. Oncotarget, 6(7), 4953–4967. <a href="https://doi.org/10.18632/oncotarget.3211">https://doi.org/10.18632/oncotarget.3211</a></li>
<li class="show">Van Pham, P. (2016). Clinical application of stem cells: An update 2015. Biomedical Research and Therapy, 3(2), 483–489. <a href="https://doi.org/10.7603/s40730-016-0005-9">https://doi.org/10.7603/s40730-016-0005-9</a></li>
<li class="show">Wang, J., Cen, P., Chen, J., Fan, L., Li, J., Cao, H., & Li, L. (2017). Role of mesenchymal stem cells, their derived factors, and extracellular vesicles in liver failure. Stem Cell Research & Therapy, 8(1), 137. <a href="https://doi.org/10.1186/s13287-017-0576-4">https://doi.org/10.1186/s13287-017-0576-4</a></li>
<li class="show">Wang, L., Gu, Z., Zhao, X., Yang, N., Wang, F., Deng, A., . . . Gao, C. (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 and Development, 25(24), 1874–1883. <a href="https://doi.org/10.1089/scd.2016.0107">https://doi.org/10.1089/scd.2016.0107</a></li>
<li class="show">Yañez, R., Lamana, M. L., García-Castro, J., Colmenero, I., Ramírez, M., & Bueren, J. A. (2006). Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells (Dayton, Ohio), 24(11), 2582–2591. <a href="https://doi.org/10.1089/scd.2016.0107">https://doi.org/10.1634/stemcells.2006-0228</a></li>
<li class="show">Yáñez-Mó, M., Siljander, P. R., Andreu, Z., Zavec, A. B., Borràs, F. E., Buzas, E. I., . . . De Wever, O. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1), 27066. <a href="https://doi.org/10.3402/jev.v4.27066">https://doi.org/10.3402/jev.v4.27066</a></li>
<li class="show">Yu, B., Zhang, X., & Li, X. (2014). Exosomes derived from mesenchymal stem cells. International Journal of Molecular Sciences, 15(3), 4142–4157. <a href="https://doi.org/10.3390/ijms15034142">https://doi.org/10.3390/ijms15034142</a></li>
<li class="show">Yuan, Z., Kolluri, K. K., Gowers, K. H. C., & Janes, S. M. (2017). TRAIL delivery by MSC-derived extracellular vesicles is an effective anticancer therapy. Journal of Extracellular Vesicles, 6(1), 1265291. <a href="https://doi.org/10.1080/20013078.2017.1265291">https://doi.org/10.1080/20013078.2017.1265291</a></li>
<li class="show">Zhang, B., Wang, M., Gong, A., Zhang, X., Wu, X., Zhu, Y., . . . Xu, W. (2015a). HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells (Dayton, Ohio), 33(7), 2158–2168. <a href="https://doi.org/10.1002/stem.1771">https://doi.org/10.1002/stem.1771</a></li>
<li class="show">Zhang, B., Wu, X., Zhang, X., Sun, Y., Yan, Y., Shi, H., . . . Xu, W. (2015b). Human umbilical cord mesenchymal stem cell exosomes enhance angiogenesis through the Wnt4/β-catenin pathway. Stem Cells Translational Medicine, 4(5), 513–522.<a href=" https://doi.org/10.5966/sctm.2014-0267"> https://doi.org/10.5966/sctm.2014-0267</a></li>
<li class="show">Zhang, B., Yin, Y., Lai, R. C., Tan, S. S., Choo, A. B., & Lim, S. K. (2014). Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells and Development, 23(11), 1233–1244. <a href="https://doi.org/10.1089/scd.2013.0479">https://doi.org/10.1089/scd.2013.0479</a></li>
<li class="show">Zhang, S., Chu, W. C., Lai, R. C., Lim, S. K., Hui, J. H., & Toh, W. S. (2016). Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis and Cartilage, 24(12), 2135–2140. <a href="https://doi.org/10.1016/j.joca.2016.06.022">https://doi.org/10.1016/j.joca.2016.06.022</a></li>
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2017-08-28
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Concise review: Extracellular vesicles from mesenchymal stem cells as cellular therapy. (2017). Biomedical Research and Therapy, 4(08), 1562-1573. https://doi.org/10.15419/bmrat.v4i08.287
