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

Lavasani, M and Robinson, AR and Lu, A and Song, M and Feduska, JM and Ahani, B and Tilstra, JS and Feldman, CH and Robbins, PD and Niedernhofer, LJ and Huard, J (2012) Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nature Communications, 3.

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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. © 2012 Macmillan Publishers Limited. All rights reserved.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Lavasani, M
Robinson, AR
Lu, A
Song, M
Feduska, JM
Ahani, B
Tilstra, JStilstraj@pitt.eduTILSTRAJ
Feldman, CH
Robbins, PDprobb@pitt.eduPROBB
Niedernhofer, LJniedernh@pitt.eduNIEDERNH
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 13 February 2012
Date Type: Publication
Journal or Publication Title: Nature Communications
Volume: 3
DOI or Unique Handle: 10.1038/ncomms1611
Schools and Programs: Graduate School of Public Health > Human Genetics
School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Orthopaedic Surgery
Refereed: Yes
MeSH Headings: Animals; Antigens, CD34--biosynthesis; Antigens, Ly--metabolism; Cell Differentiation; Cell Proliferation; Coculture Techniques; Collagen--metabolism; DNA Repair; Disease Models, Animal; Genotype; Humans; Longevity; Membrane Proteins--metabolism; Mice; Mice, Transgenic; Muscles--metabolism; Mutation; Osteocytes--cytology; Peroxisome Proliferator-Activated Receptors--metabolism; Progeria--genetics; Progeria--pathology; Stem Cells--cytology
Other ID: NLM PMC3272577
PubMed Central ID: PMC3272577
PubMed ID: 22215083
Date Deposited: 04 Apr 2014 15:48
Last Modified: 03 Feb 2019 06:55


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