Human clonal mesenchymal stem cells alleviated acute pancreatitis by inhibiting inflammatory response

초록

Mesenchymal stem cells (MSCs) have attracted significant attention because of their immunomdulatory function and potential therapeutic effect for autoimmune diseases. Recently we developed a novel method to isolate clonal marrow stem cells (cMSCs) from bone marrow aspirates, called subfractionation culturing method (SCM) to obtain highly homogeneous populations of MSCs. Human cMSCs (hcMSCs) were isolated with human BM aspirates using the SCM and a library of hcMSC lines was established. Using these hcMSCs, we investigated whether these hcMSCs can treat acute pancreatitis (AP). AP is a disease with a high mortality rate, and repetitive AP induces chronic AP and pancreatic adenocarcinoma. In this study, we investigated whether hcMSCs have potential therapeutic effects in both mild- and severe-AP. Mild-AP was induced by thrice intraperitoneal (i.p.) injections of cerulein (100 μg/kg) and severe-AP by intraparenchymal injection of 3% sodium taurocholate solution (TCA) in Sprague-Dawley (SD) rats. hcMSCs (1x106) were labeled with CM-DiI and infused by tail vein. Much more of the systemic infusions of hcMSCs were detected in the pancreas of rats with mild- and severe-AP than in those of normal rats. Infused hcMSCs ameliorated acinar cell degeneration, pancreatic edema, and inflammatory infiltration in both pancreatitis models. Also, hcMSCs reduced expression levels of inflammation mediators and cytokines in both mild- and severe-AP. In addition, hcMSCs decreased T cell infiltration and increased expression of Foxp3+ regulatory T cell in vitro and in vivo. Our results show that hcMSCs may repair AP by inhibiting inflammatory mediators and cytokines through generation of Foxp3+ regulatory T cell. We suggest that hcMSCs can be considered as an attractive candidate for a stem cell-based AP therapy.