Bone marrow-derived mesenchymal stem cells attenuate severe acute pancreatitis via regulation of microRNA-9 to inhibit necroptosis in rats

• Published in: Life sciences (1973) 2019-04, Vol.223, p.9-21
• Main Authors: Song, Guodong, Ma, Zhilong, Liu, Dalu, Qian, Daohai, Zhou, Jia, Meng, Hongbo, Zhou, Bo, Song, Zhenshun
• Format: Article
• Language: English
• Subjects: Acinar cells; Animal models; BMSCs; Bone marrow; Digestive system; Inflammation; Inflammatory response; Injury prevention; Kinases; Mesenchymal stem cells; Mesenchyme; MicroRNAs; miR-9; miRNA; Necroptosis; Pancreas; Pancreatic islet transplantation; Pancreatitis; Protein kinase; Proteins; Regeneration; Ribonucleic acid; RIPK1; RNA; SAP; Signal transduction; Stem cell transplantation; Stem cells; Tissues; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.03.019

Severe acute pancreatitis (SAP) is an acute disease of the digestive system accompanied by pancreatic necrosis. We have found that bone marrow-derived mesenchymal stem cells (BMSCs) can attenuate SAP, but the underlying mechanism remains unclear. The present study was conducted to explore the possible mechanisms by which BMSCs alleviate SAP. BMSCs and BMSCs engineered to overexpress microRNA (miR)-9 (miR-9-BMSCs) were transplanted into rat models of SAP via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreatic tissues and induced by tumor necrosis factor-α (TNF-α) in vitro. miR-9-BMSCs significantly reduced the systemic inflammatory response, impeded the necroptosis signaling pathway and promoted regeneration of damaged pancreas in vivo. miR-9-BMSCs secreted miR-9, which targeted the gene encoding receptor interacting protein kinase 1 in PACs induced by TNF-α, to inhibit necroptosis and ameliorate SAP. miR-9-BMSCs can reduce SAP-induced injury to pancreatic tissues and PACs by regulating miR-9 to suppress necroptosis.