Therapeutic effect of human umbilical cord-derived mesenchymal stem cells in rat severe acute pancreatitis.

ABSTRACT

AIM: To investigate the therapeutic effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on rat severe acute pancreatitis (SAP). METHODS: Rats were randomly divided into three groups (n = 15 per group) control group, SAP group, and SAP+MSCs group. SAP was established by retrograde pancreatic duct injection of 3% sodium taurocholate. In SAP+MSCs group, UC-MSCs at 1 × 10(7) cells/kg were injected via the tail vein 12 h after SAP. Rats (n = 5 per group) were sacrificed on days 1, 3 and 5, and the blood and pancreatic tissues were collected. The levels of serum amylase, lipase, inflammatory cytokines, and anti-inflammatory cytokines were determined. Pathological changes of the pancreas (HE staining) and apoptotic acinar cells (TUNEL staining) were observed under light microscope. RESULTS: The levels of serum amylase and lipase in SAP group were significantly higher than those in control group (P<0.05). The pancreas in SAP group showed significantly massive edema, inflammation, hemorrhage and necrosis when compared with control group. There were numerous TUNEL-positive apoptotic acinar cells after SAP. However, in SAP+MSCs group, the levels of serum amylase were significantly reduced on days 1, 3, and 5 after MSC transplantation (P<0.01). The serum lipase level in SAP+MSCs group was significantly lower than that in SAP group on days 3 and 5 (P<0.01). The edema formation, inflammatory cell infiltration, hemorrhage, and necrosis were reduced significantly attenuated in SAP+MSCs group as compared to SAP group (P<0.05). MSCs significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), but increased the levels of anti-inflammatory cytokines (IL-4 and IL-10) in SAP rats. The number of TUNEL-positive acinar cells was significantly reduced on days 3 and 5 after MSCs transplantation (P<0.01). CONCLUSION: Transplantation of UC-MSCs significantly inhibits inflammation and decreases pancreatic injury secondary to SAP.