Abstract
SummarySarcopenia 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.
Highlights
Sarcopenia is the age-related loss of muscle mass, strength, and function (Delbono, 2011)
Our results showed that Alkaline phosphatase (ALP)+/CD15– cells displayed the capacity to form both myotubes and adipocytes (% Oil Red O area vs. total area = 9.9% Æ 2.7), whereas ALP+/CD15+ and ALP–/CD15– cells showed no differentiation potential to the myogenic lineage (Figure 2c) and only a limited capacity toward adipogenic commitment (Figure 2d)
These results showed that aging leads to a decline of multipotency in MABs and suggested that an adipogenic alternative program might be more pronounced in elderly MABs
Summary
Sarcopenia is the age-related loss of muscle mass, strength, and function (Delbono, 2011). FAPs have been shown to possess an adipogenic potential in vitro and in vivo and are currently isolated in mice as Sca1+, or Pdgfra+ (platelet-derived growth factor receptor alpha) cells since these two populations are considered equivalent (Joe et al, 2010; Uezumi et al, 2010). Traktuev et al identified a specific group of CD34+ adipogenic stem cells (ASCs) that possess pericyte properties, due to their expression of NG2 (neural/glial antigen 2), aSMA (alpha smooth muscle actin), and PDGFRb (platelet-derived growth factor receptor beta). This population has been shown to localize in vessels at the interface between endothelium and adipocytes, supporting endothelial survival (Traktuev et al, 2008). We focused our attention on young/elderly MABs, referred here as ALP+ CD15– cells, comparing their in vitro and in vivo differentiation capability
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