Decreased immunomodulatory and secretory capability of aging human umbilical cord mesenchymal stem cells in vitro.

Mesenchymal stem cell therapy has drawn much attention as a promising therapeutic option for the treatment of different diseases. Due to insufficient cell population derived from freshly isolated tissues, in vitro propagation is required prior to clinical use. However, reduced cell viability of aging mesenchymal stem cell (MSCs) with repeated propagations has yet not be fully investigated, especially for the biological characteristics of immunoregulatory ability and paracrine factors. In this study, we compared the biological properties of human umbilical cord-MSCs (hUC-MSCs) at different passages, especially for immunomodulatory ability and secretions. Our results showed that hUC-MSCs at early passage (P2) and late passage (P8) exhibited similar morphology and surface marker expression, but hUC-MSCs at P8 displayed reduced proliferation and differentiation potential, immunoregulatory and secretory ability. In particular, hUC-MSCs at P2 and P5 could significantly suppress the population of proinflammatory Th1 and Th17 cell subsets and upregulate Treg cells, but not with hUC-MSCs at P8. For paracrine mechanism, higher level of secretions such as growth factors, cell adhesions, anti-inflammatory factors of hUC-MSCs were observed at P2 and P5 compared to that at P8. Therefore, it is essential to verify and validate the biological characteristics of hUC-MSCs that possess a good vitality before they are released for clinical use. Altogether, this study provides a rationale and two important parameters for how to select appropriate passage and vitality of MSCs for cell therapy.