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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 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.