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

Mitra Lavasani, Andria R. Robinson, Aiping Lu, Minjung Song, Joseph M. Feduska, Bahar Ahani, Jeremy S. Tilstra, Chelsea H. Feldman, Paul D. Robbins, Laura J. Niedernhofer () and Johnny Huard ()
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Mitra Lavasani: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
Andria R. Robinson: University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
Aiping Lu: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
Minjung Song: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
Joseph M. Feduska: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
Bahar Ahani: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
Jeremy S. Tilstra: University of Pittsburgh School of Medicine
Chelsea H. Feldman: University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
Paul D. Robbins: University of Pittsburgh School of Medicine
Laura J. Niedernhofer: University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
Johnny Huard: Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms1611

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