Substance P blocks the impairment of paracrine potential of MSC due to long term culture

Backgrounds Transplantation of mesenchymal stem cells (MSCs) has been considered a novel cell therapy for diverse diseases. MSCs exert their effect through multi-lineage differentiation, immunosuppression, and anti-apoptosis, as proven in diseases like diabetes or rheumatoid arthritis. However, transplantation of MSCs has some limitations; donor age plays an important role in determining their therapeutic activity. Aged MSCs have low proliferative and paracrine potential. Moreover, long-term culture in vitro triggers cellular senescence. Thus, a strategy to enhance cellular activity and block senescence during ex vivo culture is needed to develop efficacious MSC-based therapies. Methods In this study, we examined the beneficial role of Substance P (SP) on paracrine activity in human bone marrow-derived MSCs from young or aged donors. During ex vivo culture, MSCs were treated with SP and their proliferation rates, cumulative cell numbers, cytokine profiles, and multi-differentiation abilities were analyzed. Results In MSCs derived from young donors, longterm culture inhibited proliferation and cytokine secretion (TGF-β and VEGF), which were alleviated by the addition of SP. SP had a marked positive effect on the activity of aged MSCs. Conclusion Collectively, SP can block the loss of therapeutic potential of MSCs by preserving their proliferative and paracrine potential. This study indicates the potential of SP as a supplement in stem cell culture for therapy.