Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration
Copyright policy )Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration
Abstract Introduction Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle. Methods We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24-/-) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function. Results Our results indicate that MDSPCs isolated from Zmpste24-/- mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24-/- MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24-/- MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro. Conclusions These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells.
- University of Pittsburgh School of Medicine United States
- University of Pittsburgh United States
- UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- University of Pittsburgh School of Medicine United States
Research, Stem Cells, Membrane Proteins, Metalloendopeptidases, Cell Differentiation, Mice, SCID, Lamin Type A, Coculture Techniques, Mice, Inbred C57BL, Mice, Phenotype, Animals, Regeneration, Transplantation, Homologous, Muscle, Skeletal, Cell Proliferation, Stem Cell Transplantation
Research, Stem Cells, Membrane Proteins, Metalloendopeptidases, Cell Differentiation, Mice, SCID, Lamin Type A, Coculture Techniques, Mice, Inbred C57BL, Mice, Phenotype, Animals, Regeneration, Transplantation, Homologous, Muscle, Skeletal, Cell Proliferation, Stem Cell Transplantation
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