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Induced pluripotent stem cells attenuate chronic allogeneic vasculopathy in an integrin beta‐1‐dependent manner
Author(s) -
Lu Meng,
Xue Rong,
Wang Pingping,
Wang Xiaokai,
Tian Xiaoyu,
Liu Yingying,
Wang Shun,
Cui Anfeng,
Xie Jingxin,
Le Lili,
Zhao Meng,
Quan Jing,
Li Ning,
Meng Dan,
Wang Xinhong,
Sun Ning,
Chen Alex F.,
Xiang Meng,
Chen Sifeng
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15900
Subject(s) - induced pluripotent stem cell , homing (biology) , medicine , embryonic stem cell , endothelial stem cell , small interfering rna , microbiology and biotechnology , integrin , transfection , stem cell , cancer research , immunology , biology , cell culture , in vitro , receptor , biochemistry , ecology , genetics , gene
This study aimed to determine the mechanism of isogeneic‐induced pluripotent stem cells (iPSCs) homing to vascular transplants and their therapeutic effect on chronic allogeneic vasculopathy. We found that integrin β1 (Intgβ1) was the dominant integrin β unit in iPSCs that mediates the adhesion of circulatory and endothelial cells (ECs). Intgβ1 knockout or Intgβ1‐siRNAs inhibit iPSC adhesion and migration across activated endothelial monolayers. The therapeutic effects of the following were examined: iPSCs, Intgβ1‐knockout iPSCs, iPSCs transfected with Intgβ1‐siRNAs or nontargeting siRNAs, iPSC‐derived ECs, iPSC‐derived ECs simultaneously overexpressing Intgα4 and Intgβ1, iPSCs precultured in endothelial medium for 3 days (endothelial‐prone stem cells), primary aortic ECs, mouse embryonic fibroblasts, and phosphate‐buffered saline (control). The cells were administered every 3 days for a period of 8 weeks. iPSCs, iPSCs transfected with nontargeting siRNAs, and endothelial‐prone stem cells selectively homed on the luminal surface of the allografts, differentiated into ECs, and decreased neointimal proliferation. Through a single administration, we found that iPSCs trafficked to allograft lesions, differentiated into ECs within 1 week, and survived for 4‐8 weeks. The therapeutic effect of a single administration was moderate. Thus, Intgβ1 and pluripotency are essential for iPSCs to treat allogeneic vasculopathy.