Aging affects the in vivo regenerative potential of human mesoangioblasts |
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Authors: | Alessio Rotini Ester Martínez‐Sarrà Robin Duelen Domiziana Costamagna Ester Sara Di Filippo Giorgia Giacomazzi Hanne Grosemans Stefania Fulle Maurilio Sampaolesi |
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Institution: | 1. Translational Cardiomyology Laboratory, Stem Cell Institute of Leuven, Unit of Stem Cell Research, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, University of Leuven, Leuven, Belgium;2. Department of Neuroscience, Imaging and Clinical Sciences, University “G. d'Annunzio” Chieti‐Pescara, Chieti, Italy;3. Interuniversity Institute of Myology, Chieti, Italy;4. Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy |
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Abstract: | Sarcopenia is the age‐related loss of muscle mass, strength, and function. Although the role of human satellite cells (SCs) as adult skeletal muscle stem cells has been deeply investigated, little is known about the impact of aging on muscle interstitial stem cells. Here, we isolated the non‐SC CD56– fraction from human muscle biopsies of young and elderly subjects. The elderly interstitial cell population contained a higher number of CD15+ and PDGFRα+ cells when compared to young samples. In addition, we found that the CD56–/ALP+ cells were well represented as a multipotent stem cell population inside the CD56– fraction. CD56–/ALP+/CD15– cells were clonogenic, and since they were myogenic and expressed NG2, α‐SMA and PDGFRβ can be considered mesoangioblasts (MABs). Interestingly, elderly MABs displayed a dramatic impairment in the myogenic differentiation ability in vitro and when transplanted in dystrophic immunodeficient Sgcb‐null Rag2‐null γc‐null mice. In addition, elderly MABs proliferated less, but yet retained other multilineage capabilities. Overall, our results indicate that aging negatively impacted on the regenerative potential of MABs and this should be carefully considered for potential therapeutic applications of MABs. |
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Keywords: | aging muscular dystrophy myogenic differentiation potential sarcopenia skeletal muscle and myopathies |
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