Repeated pluripotent stem cell administration delays age-associated decline in mice

Background: Yamanaka-factor-mediated partial reprogramming(definition) can reverse selected age-associated changes without complete loss of cellular identity.We asked whether repeated systemic administration of intact human pluripotent stem cells, which maintain pluripotency-associated networks, might similarly influence age-related decline.Methods: Female immunodeficient mice were allocated to vehicle control, human amnion-derived mesenchymal stem cell, or human pluripotent stem cell groups (n = 6 per group).From 14 weeks of age, mice received 14 approximately monthly intravenous administrations of vehicle or 1 × 10 5 cells and were followed to 79 weeks.Survival, body weight, spontaneous movement, and serum biochemistry were assessed.Results: Survival declined earlier in the vehicle and mesenchymal stem cell groups.The pluripotent stem cell group maintained 100% survival until week 78, when two mice died; four of six mice (66.7%) remained alive at study termination at week 79.Mean distance traveled during 10 seconds was 19.1, 89.2, and 107.0 cm in the vehicle, mesenchymal stem cell, and pluripotent stem cell groups, respectively; both cell-treated groups exceeded the vehicle group.Body weight remained relatively stable.At 79 weeks, the pluripotent stem cell group generally showed lower renal, hepatic, lipid, and metabolic biochemical values than the other aged groups.Conclusions: Repeated pluripotent stem cell administration was associated with a later onset of survival decline, greater spontaneous movement at the terminal assessment, and favorable late-life biochemical patterns.These exploratory findings support mechanistic studies testing whether factors released by pluripotent stem cells can modify aging-related processes.