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

Author

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  • Mitra Lavasani

    (Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
    University of Pittsburgh School of Medicine)

  • Andria R. Robinson

    (University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
    University of Pittsburgh Graduate School of Public Health)

  • Aiping Lu

    (Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
    University of Pittsburgh School of Medicine)

  • Minjung Song

    (Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
    University of Pittsburgh School of Medicine)

  • 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
    University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
    University of Pittsburgh School of Medicine)

  • Laura J. Niedernhofer

    (University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center 2.6
    University of Pittsburgh School of Medicine)

  • Johnny Huard

    (Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive
    University of Pittsburgh School of Medicine
    University of Pittsburgh School of Medicine)

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.

Suggested Citation

  • 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 & Johnny Huard, 2012. "Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1611
    DOI: 10.1038/ncomms1611
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