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Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model.


ABSTRACT: With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspan extension. The transplanted MDSPCs improve degenerative changes and vascularization in tissues where donor cells are not detected, suggesting that their therapeutic effect may be mediated by secreted factor(s). Indeed, young wild-type-MDSPCs rescue proliferation and differentiation defects of aged MDSPCs when co-cultured. These results establish that adult stem/progenitor cell dysfunction contributes to ageing-related degeneration and suggests a therapeutic potential of post-natal stem cells to extend health.

SUBMITTER: Lavasani M 

PROVIDER: S-EPMC3272577 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model.

Lavasani Mitra M   Robinson Andria R AR   Lu Aiping A   Song Minjung M   Feduska Joseph M JM   Ahani Bahar B   Tilstra Jeremy S JS   Feldman Chelsea H CH   Robbins Paul D PD   Niedernhofer Laura J LJ   Huard Johnny J  

Nature communications 20120103


With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspa  ...[more]

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