Mesenchymal stem cells improve intestinal integrity during severe acute pancreatitis

Abstract

Severe acute pancreatitis (SAP) is an acute inflammatory disease of the pancreas that involves various distant tissues and organs. This study aimed to investigate post-tissue injury repair by mesenchymal stem cells (MSCs) in a rat model of SAP. A total of 54 pathogen-free adult male SD rats were randomly assigned to the groups SAP, SAP + MSCs and sham-operated (SO). SAP was induced by 4% sodium taurocholate, and MSCs were injected via the dorsal penile vein 1 h later. The amylase activity, and tumor necrosis factor (TNF)-α and diamine oxidase (DAO) levels were measured with an enzyme-linked immunosorbent assay (ELISA), while the expression of aquaporin (AQP)-1 was evaluated by immunohistochemical staining. The pathological score of intestinal tissues was also compared among groups. Marked improvement in intestinal necrosis, villi shedding and infiltration of inflammatory cells was observed in the SAP + MSCs group compared to the SAP and SO groups. Amylase, TNF-α, and DAO levels were significantly increased in the SAP + MSCs group. The intestinal expression of AQP-1 was increased at 12 and 24 h post-MSC transplantation compared to the SO group. Rats of the SAP + MSCs group displayed higher pathological scores compared to the SAP group at all time points. Overall, these data showed that MSCs can inhibit systemic inflammation and reduce TNF-α release in a rat model of SAP-induced intestinal injury, suggesting that MSCs exert protective effects on the intestinal barrier during SAP.

RETRACTED ARTICLE: MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats

“…The current treatment methods are mostly combinations of internal medicine and surgery [ 2 ]. Biotherapy, which is gradually being accepted by patients, is based on stem cells as a novel therapeutic method that is expected to cure SAP completely [ 4 , 6 , 15 – 17 , 29 – 31 ]. MSCs, which are important members of the family of stem cells, are characterized by specific properties such as self-renewal, multilineage differentiation, immunosuppressive effects, and paracrine effects and are also used as vectors for exogenous genes [ 31 ].…”

Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review

“…Since acute pancreatitis is a self-limited condition and pancreatic tissue damage occurs only following severe acute pancreatitis, all included studies investigated the effect of MSC therapy in severe acute pancreatitis. Multiple methods of inducing severe acute pancreatitis were used: injection of Na-taurocholate (7 studies) [ 44 , 46 , 47 , 49 , 50 , 52 ], intraperitoneal injections of caerulein (2 studies) [ 29 , 30 ], L-arginine-induced acute pancreatitis (one study) [ 33 ], and deoxy-STC injection under the pancreatic capsule (1 study) [ 51 ]. All 16 studies showed a reduction in pancreatic tissue damage, necrosis, inflammation, and oedema compared to those of the untreated groups.…”

“…Eleven of the 16 studies used BM-MSCs as therapy for severe acute pancreatitis [ 44 – 52 ]. Except for two studies [ 51 , 52 ], well-characterized MSCs were infused into animals using defined surface markers and mesodermal differentiation according to the criteria of the International Society for Cell Therapy. Nine of the 11 studies further evaluated the mechanism of action of BM-MSCs following severe acute pancreatitis [ 44 – 49 , 52 ].…”

Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats

“…First, the vectors of pri-miR-9-PCDH, PLKO.1-TuD or PCDH ( 8   µg/plate ), pCMVΔ R8.74 expressing HIV gag/pol, Rev and tat ( 5.3   µg/plate ), and pMD2.G expressing VSV-G ( 2.65   µg/plate ) were co-transfected into HEK293T cells by Lipo2000 as previously described 62 . Second, the supernatants were collected at 24 and 48 hr respectively and concentrated by PEG-it Virus Precipitation Solution ( System Biosciences, CA, USA ) or supercentrifugation ( 75,000   ×   g, 2 hr ).…”