Exosomes Derived from Human Induced Pluripotent Stem Cells-Endothelia Cells Promotes Postnatal Angiogenesis in Mice Bearing Ischemic Limbs
Exosomes Derived from Human Induced Pluripotent Stem Cells-Endothelia Cells Promotes Postnatal Angiogenesis in Mice Bearing Ischemic Limbs
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DOI：
10.7150/ijbs.28392
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发表时间：
2019
影响因子：
9.2
通讯作者：
Lan Zhang
中科院分区：
文献类型：
--
作者：
Meng Ye;Qihong Ni;Haozhe Qi;Xin Qian;Jiaquan Chen;Xiangjiang Guo;Maoran Li;Yiping Zhao;Guanhua Xue;Haoyu Deng;Lan Zhang
Induced pluripotent stem cell (iPSC) derived endothelial cells (ECs) is a novel therapeutic option for ischemic diseases. Although the detailed mechanism of this novel therapy remains unknown, emerging evidence has demonstrated that exosomes derived from hiPSC-ECs play a critical role in this approach. In this study, we first isolated and characterized the exosomes from iPSCs-ECs (hiPSC-EC-Exo) and determined the functional roles of hiPSC-EC-Exo in neovascularization and the underlying mechanism. Further, we evaluated the effect of exosomes derived from hiPS-ECs on promoting angiogenesis in a mouse model bearing ischemic limbs. Our results showed that miR-199b-5p, an miRNA highly associated with angiogenesis, is significantly upregulated during the differentiation of hiPSC-ECs. Mechanically, our studies found that hiPSC-ECs expressing miR-199b-5p significantly promote cell migration, proliferation and tube formation through Jagged-1-dependent upregulation of VEGFR2 in HUVECs. Similarly, coculture of hiPSC-ECs-Exo with HUVECs also resulted in a significant improvement in HUVEC migration, proliferation, and tube formation, suggesting that exosome-mediated cell-cell communication in a paracrine manner may serve as a fundamental mechanism for iPSC-EC-based treatment. Consequently, we found that the transfer of hiPSC-ECs enriched with miR-199b-5p significantly enhanced micro-vessel density and blood perfusion in ischemic limbs in vivo. Taken together, our studies were the first to demonstrate that transfer of hiPSC-ECs-Exo is a promising approach to treat ischemic injury via the mechanism of promoting neovascularization.
