Exosomes Secreted by Human iPSC-Derived Mesenchymal Stem Cells Reduce Limb Ischemia by Promoting Angiogenesis; May Represent Novel Treatment for Ischemic Diseases

Patient-specific induced pluripotent stem cells (iPSCs) are attractive because they can be an abundant source of cells that can be used for cell therapy without posing the risk of immune rejection. Studies have showed that iPSCs-derived mesenchymal stem cells (iMSCs) possess powerful proliferation, differentiation, and therapeutic effects. Recently, most studies have indicated that stem cells exert their therapeutic effect mainly through a paracrine mechanism other than transdifferentiation, and exosomes have emerged as an important paracrine factor for influencing stem cells to reprogram injured cells. The objective of the current study by scientists in China was to evaluate whether exosomes derived from iMSCs (iMSCs-Exo) possess the ability to attenuate limb ischemia and promote angiogenesis after transplantation into limbs of mice suffering from femoral artery excision. The report of this study was published online on April 10, 2015 in an open-access article in Stem Cell Research & Therapy. The article was titled “Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Attenuate Limb Ischemia by Promoting Angiogenesis.” In the work, human iPSCs (iPS-S-01, C1P33, and PCKDSF001C1) were used to differentiate into iMSCs in a modified one-step method. iMSCs were characterized by flow cytometry and multipotent differentiation potential analysis. Ultrafiltration combined purification method was used to isolate iMSCs-Exo; while transmission electron microscopy and Western blotting were used to identify iMSCs-Exo. After establishment of mouse hind-limb ischemia with excision of the femoral artery and iMSCs-Exo injection, blood perfusion was monitored at days 0, 7, 14, and 21; microvessel density in ischemic muscle was also analyzed.
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