Abstract
Adipose‐derived mesenchymal stem cell (ADSC)‐based regenerative therapies have shown potential for use in many chronic diseases. Aging diminishes stem cell regenerative potential, yet it is unknown whether stem cells from aged donors cause adverse effects in recipients. ADSCs can be obtained using minimally invasive approaches and possess low immunogenicity. Nevertheless, we found that transplanting ADSCs from old donors, but not those from young donors, induces physical dysfunction in older recipient mice. Using single‐cell transcriptomic analysis, we identified a naturally occurring senescent cell‐like population in ADSCs primarily from old donors that resembles in vitro‐generated senescent cells with regard to a number of key pathways. Our study reveals a previously unrecognized health concern due to ADSCs from old donors and lays the foundation for a new avenue of research to devise interventions to reduce harmful effects of ADSCs from old donors.
Highlights
No statistically significant differences were observed in terms of treadmill, body weight change, food intake, or remaining lifespan (Figure S1a-d), which might be due to an insufficient number of transplanted old Adipose-derived mesenchymal stem cell (ADSC) to cause detectible changes in these tests. These findings suggest that ADSCs from old donors can induce physical frailty, which is highly associated with morbidity and loss of independence(Ensrud et al, 2009)
We demonstrated that transplanting a small number of in vitro-generated senescent ADSCs (stable proliferative arrest caused by various stresses (Campisi & d'Adda di Fagagna, 2007) induces physical dysfunction in mice (Xu et al, 2018)
We found that 8.9% of cells from old donors were p21high compared with 3% of cells in young donors (Figure 2a), both of which are similar to the percentages of senescent cells observed in ADSCs isolated from young and old human donors (Xu et al, 2015)
Summary
We transplanted 1 x 106 ADSCs from young or old donors i.p. into syngeneic 20-month-old C57BL/6 male mice (Figure 1a). We demonstrated that transplanting a small number of in vitro-generated senescent ADSCs (stable proliferative arrest caused by various stresses (Campisi & d'Adda di Fagagna, 2007) induces physical dysfunction in mice (Xu et al, 2018).
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