Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model.
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.
Stem Cell Research Center, 206 Bridgeside Point II, 450 Technology Drive, Pittsburgh, Pennsylvania 15219, USA.
Mitra
M
Lavasani
Andria R
AR
Robinson
Aiping
A
Lu
Minjung
M
Song
Joseph M
JM
Feduska
Bahar
B
Ahani
Jeremy S
JS
Tilstra
Chelsea H
CH
Feldman
Paul D
PD
Robbins
Laura J
LJ
Niedernhofer
Johnny
J
Huard
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004260:DNA Repair; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D008136:Longevity; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D010011:Osteocytes / Q000166:cytology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011371:Progeria / Q000235:genetics* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*
D018952:Antigens, CD34; D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D003094:Collagen