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-beta 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.