Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 1, Pages 695-710Publisher
WILEY
DOI: 10.1111/jcmm.14778
Keywords
exosome; immune rejection; ischaemic hindlimb repair; mesenchymal stem cell; miRNA; survival
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Funding
- National Natural Science Foundation of China (NSFC) [81870194, 91849122, 91839101]
- Jiangsu Province Peak of Talent in Six Industries [BU24600117]
- National Natural Science Foundation of China [U1601227]
- Science and Technology Programs of Guangdong Province [2015B020225006]
- Introduction project of clinical medicine expert team for Suzhou [SZYJTD201704]
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Generating universal human umbilical mesenchymal stem cells (UMSCs) without immune rejection is desirable for clinical application. Here we developed an innovative strategy using CRISPR/Cas9 to generate B2M(-)UMSCs in which human leucocyte antigen (HLA) light chain beta 2-microglobulin (B2M) was deleted. The therapeutic potential of B2M(-)UMSCs was examined in a mouse ischaemic hindlimb model. We show that B2M(-)UMSCs facilitated perfusion recovery and enhanced running capability, without inducing immune rejection. The beneficial effect was mediated by exosomes. Mechanistically, microRNA (miR) sequencing identified miR-24 as a major component of the exosomes originating from B2M(-)UMSCs. We identified Bim as a potential target of miR-24 through bioinformatics analysis, which was further confirmed by loss-of-function and gain-of-function approaches. Taken together, our data revealed that knockout of B2M is a convenient and efficient strategy to prevent UMSCs-induced immune rejection, and it provides a universal clinical-scale cell source for tissue repair and regeneration without the need for HLA matching in the future.
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