New therapeutic approach for acute pancreatitis

Background & Aims: Acute pancreatitis (AP) is a disease with a high mortality rate, and repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunomodulatory roles and beneficial effects on various inflammation-based diseases. In this study, we investigated whether human bone marrow-derived clonal mesenchymal stem cells (hcMSCs), isolated from human bone marrow aspirate according to our newly established isolation protocol have potential therapeutic effects in both mild- and severe-AP. Methods: Mild-AP was induced by thrice intraperitoneal (i.p.) injections of cerulein (100 μg/kg) at 2 h intervals in Sprague-Dawley (SD) rats. Severe-AP was induced by intraparenchymal injection of 3% sodium taurocholate solution (TCA) in rats. hcMSCs (1x10⁶) were labeled with CM-DiI and infused by tail vein. Results: hcMSCs exhibited self-renewal, multipotential differentiation capacities, and immunomodulatory functions. 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.

Conclusion: Our results show that hcMSCs may repair AP by inhibiting inflammatory mediators and cytokines through generation of Foxp3⁺ regulatory T cells. We suggest that hcMSCs can be considered as an attractive candidate for a cell-based AP therapy.

P/S  Latter part of this lecture will be covered by the topic for development of new PI3K inhibitor as a anticancer drug.