Ic mesenchymal stem cell therapies. Hum Gene Ther. 2010;21:1641?5. 11. Xin Y, Wang YM, Zhang H, Li J, Wang W, Wei YJ, et al. Aging adversely impacts biological properties of human bone marrow-derived mesenchymal stem cells: implications for tissue engineering heart valve Tariquidar chemical information construction. Artif Organs. 2010;34:215?2. 12. Zaim M, Karaman S, Cetin G, Isik S. Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Ann Hematol. 2012;91:1175?6. 13. Hirschi KK, Li S, Roy K. Induced pluripotent stem cells for regenerative PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28128382 medicine. Annu Rev Biomed Eng. 2014;16:277?4. 14. Diederichs S, Tuan RS. Functional comparison of human-induced pluripotent stem cell-derived mesenchymal cells and bone marrow-derived mesenchymal stromal cells from the same donor. Stem Cells Dev. 2014;23:1594?10. 15. Lian Q, Zhang Y, Zhang J, Zhang HK, Wu X, Zhang Y, et al. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation. 2010;121:1113?3. 16. Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC, et al. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65:3035?. 17. Jeong JO, Han JW, Kim JM, Cho HJ, Park C, Lee N, et al. Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circulation Res. 2011;108:1340?. 18. Ratajczak MZ, Jadczyk T, Pedziwiatr D, Wojakowski W. New advances in stem cell research: practical implications for regenerative medicine. Pol Arch Med Wewn. 2014;124:417?6. 19. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569?9. 20. Record M, Carayon K, Poirot M, Silvente-Poirot S. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta. 2014;1841:108?0.Conclusions The present study demonstrated that iMSCs-Exo transplantation can protect against ischemic injury in an experimental mouse hind-limb ischemic model. One potential mechanism for exerting the protective function of iMSCsExo was the stimulation of angiogenesis in ischemic muscle. Overall, the application of iMSCs-Exo may be a novel therapeutic approach in the treatment of ischemic disease. Additional fileAdditional file 1: Figure S1. Flow cytometric analysis of mesenchymal markers of induced pluripotent stem cells (iPSCs). Flow cytometric analysis revealed that iPSCs were positive for CD90, weakly positive for CD29 and CD34, and negative for CD44, CD45, CD73, CD105, CD133, CD146, and HLA-DR. Black histograms represent the isotype controls, and the red solid peak represents the indicated marker.Abbreviations ANOVA: analysis of variance; APC: allophycocyanin; bFGF: basic fibroblast growth factor; bFGFR: basic fibroblast growth factor receptor; BMSC: bone marrow-derived mesenchymal stem cell; BSA: bovine serum albumin; CCK-8: Cell Counting Kit-8; CI: cell-sensor impedance; ELISA: enzyme-linked immunosorbent assay; ESC: embryonic stem cell; FBS: fetal bovine serum; FIH: factor-inhibiting hypoxia-inducible factor; FITC: fluorescein isothiocyanate; HIF-1: hypoxia-inducible factor-1; HUVEC: human umbilical vein endothelial cell; iMSC: induced pluripotent stem cell-derived mesenchymal stem cell; iMSCs-Exo: exosomes derived from induced pluripotent stem cell-derived mesenchymal stem cells; iPSC: in.
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