Open AccessKnockout of beta‐2 microglobulin reduces stem cell‐induced immune rejection and enhances ischaemic hindlimb repair via exosome/miR‐24/Bim pathway
Author(s) -
Zhang Yuqing,
Wang Yanli,
Shao Lianbo,
Pan Xiangbin,
Liang Chun,
Liu Bin,
Zhang Yu,
Xie Wenping,
Yan Bing,
Liu Feng,
Yu Xiyong,
Li Yangxin
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14778
Subject(s) - immune system , mesenchymal stem cell , stem cell , microvesicles , exosome , biology , beta 2 microglobulin , microbiology and biotechnology , cancer research , microrna , immunology , genetics , gene
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 β2‐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.