Knockout of beta-2 microglobulin reduces stem cell-induced immune rejection and enhances ischaemic hindlimb repair via exosome/miR-24/Bim pathway.
J Cell Mol Med
; 24(1): 695-710, 2020 01.
Article
in En
| MEDLINE
| ID: mdl-31729180
ABSTRACT
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 ß2-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta 2-Microglobulin
/
MicroRNAs
/
Stem Cell Transplantation
/
Exosomes
/
Bcl-2-Like Protein 11
/
Hindlimb
/
Ischemia
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Cell Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Type:
Article
Affiliation country:
China