Endothelial cells, leading to an inhibition of Notch signaling and an increased capillary-like structure formation in vitro and in vivo [52]. Therefore, these results indicate that angiogenesis-related proteins and miRNAs may be the main components in exosomes to exert their pro-angiogenesis function. In our experiment, we found that iMSCs-Exo can stimulate angiogenesis-related gene expression and Naramycin A dose protein secretion. After being cultured with iMSCs-Exo, HUVECs expressed higher levels of PGF, HIF-1, TGFB1, VEGFA, VEGFB, Angiogenin, bFGF, KDR, and bFGFR and secreted more VEGF, TGFB1, and Angiogenin. These data indicated that iMSCs-Exo can activate an array of angiogenesis-related gene expression and protein secretion after their uptake by HUVECs. It has been well demonstrated that simultaneous delivery of multiple angiogenic factors is more effective than the delivery of a single angiogenic factor in enhancing vesselHu et al. Stem Cell Research Therapy 2015, 6:10 http://stemcellres.com/content/6/1/Page 14 ofdensity and maturity [53], which suggests that iMSCsExo may play a more powerful pro-angiogenesis function than that of a single recombinant angiogenic factor supplement.Research and Development Program of China (#2012AA020506), and Shanghai Jiaotong University Affiliated Sixth People’s Hospital (#1571). Author details PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28298493 1 Department of Neurosurgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. 2Jiangxi Medical College of Nanchang University, 461 BaYi Avenue, Nanchang 330006, China. 3 Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Received: 5 August 2014 Revised: 7 August 2014 Accepted: 20 January 2015 Published: 10 April 2015 References 1. Miyajima A, Tanaka M, Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell. 2014;14:561?4. 2. Volarevic V, Bojic S. Stem cells as new agents for the treatment of infertility: current and future perspectives and challenges. Biomed Res Int. 2014;2014:507234. 3. Abdelwahid E, Siminiak T, Guarita-Souza LC, de Carvalho KA T, Gallo P, Shim W, et al. Stem cell therapy in heart diseases: a review of selected new perspectives, practical considerations and clinical applications. Curr Cardiol Rev. 2011;7:201?2. 4. Choi SH, Jung SY, Kwon SM, Baek SH. Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges. Circ J. 2012;76:1307?2. 5. Gutierrez-Fernandez M, Rodriguez-Frutos B, Ramos-Cejudo J, Otero-Ortega L, Fuentes B, Diez-Tejedor E. Stem cells for brain repair and recovery after stroke. Expert Opin Biol Ther. 2013;13:1479?3. 6. van Velthoven CT, Sheldon RA, Kavelaars A, Derugin N, Vexler ZS, Willemen HL, et al. Mesenchymal stem cell transplantation attenuates brain injury after neonatal stroke. Stroke. 2013;44:1426?2. 7. Gremmels H, Fledderus JO, Teraa M, Verhaar MC. Mesenchymal stromal cells for the treatment of critical limb ischemia: context and perspective. Stem Cell Res Ther. 2013;4:140. 8. Lee EJ, Park HW, Jeon HJ, Kim HS, Chang MS. Potentiated therapeutic angiogenesis by primed human mesenchymal stem cells in a mouse model of hindlimb ischemia. Regenerative Med. 2013;8:283?3. 9. Boyle AJ, McNiece IK, Hare JM. Mesenchymal stem cell therapy for cardiac repair. Methods Mol Biol. 2010;660:65?4. 10. Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogene.
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