title: Therapeutic effect of human umbilical cord-derived mesenchymal stem cells in rat severe acute pancreatitis.
abstract: OBJECTIVE
  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-1β, 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).
  
  
  CONCLUSIONS
  Transplantation of UC-MSCs significantly inhibits inflammation and decreases pancreatic injury secondary to SAP.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Shanghai Tenth People's Hospital, Tongji University Shanghai 200072, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Meng
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Hua
authors.forename: Le
authors.initials: L
authors.lastname: Yao
authors.forename: Zhen-Shun
authors.initials: ZS
authors.lastname: Song
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007275:Injections, Intravenous; D008049:Lipase / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D013656:Taurocholic Acid; D008049:Lipase; D000681:Amylases
keywords: Umbilical cord-derived mesenchymal stem cells; apoptosis; inflammation; pancreatic pathology; severe acute pancreatitis