4.6 Article

Induced pluripotent stem cells attenuate chronic allogeneic vasculopathy in an integrin beta-1-dependent manner

期刊

AMERICAN JOURNAL OF TRANSPLANTATION
卷 20, 期 10, 页码 2755-2767

出版社

WILEY
DOI: 10.1111/ajt.15900

关键词

cell adhesion molecules; chronic transplant rejection; endothelial cells; induced pluripotent stem cells; stem cell trafficking; transplant arteriosclerosis; vascular injury

资金

  1. National Natural Science Foundation of China [91539120, 81220108002, 81970074, 81470260]
  2. National Key R&D Program of China [2016YFC1305101]

向作者/读者索取更多资源

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 beta 1 (Intg beta 1) was the dominant integrin beta unit in iPSCs that mediates the adhesion of circulatory and endothelial cells (ECs). Intg beta 1 knockout or Intg beta 1-siRNAs inhibit iPSC adhesion and migration across activated endothelial monolayers. The therapeutic effects of the following were examined: iPSCs, Intg beta 1-knockout iPSCs, iPSCs transfected with Intg beta 1-siRNAs or nontargeting siRNAs, iPSC-derived ECs, iPSC-derived ECs simultaneously overexpressing Intg alpha 4 and Intg beta 1, 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, Intg beta 1 and pluripotency are essential for iPSCs to treat allogeneic vasculopathy.

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