Metformin rejuvenates Nap1l2-impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming.

ABSTRACT: Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis

SUBMITTER: Liu F 

PROVIDER: S-EPMC11216924 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature