Metformin rejuvenates Nap1l2-impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming.
Cell Prolif
; 57(7): e13612, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38348888
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 of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encefalomielitis Autoinmune Experimental
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Inmunomodulación
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Células Madre Mesenquimatosas
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Metformina
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Cell Prolif
Año:
2024
Tipo del documento:
Article
País de afiliación:
China