Placental chorionic plate-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating macrophage polarization via secreting TSG-6

Stem Cell Research & Therapy

Lijun Tang¹  Shuai Li¹  Yi Wen¹  Xiaohui Yuan¹  Ruohong Liu¹  Bing Wang¹  Yi Yang¹  Hongyu Sun²  Qilin Huang³  Chen Luo⁴  Shuxu Yang⁵  Xiumei Cheng⁶ 

[1] Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, 610083, Chengdu, China;Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, 610083, Chengdu, China;Laboratory of Basic Medicine, The General Hospital of Western Theater Command, 610031, Chengdu, China;Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, 610083, Chengdu, China;Tianjin Medical University, 300070, Tianjin, China;Division of Hepatobiliary Pancreatic Surgery, Panzhihua Central Hospital, Sichuan Province, 617017, Panzhihua, China;Tianjin Medical University, 300070, Tianjin, China;XinDu Hospital of Traditional Chinese Medicine & Chengdu 2nd Hospital of Traditional Chinese Medicine, 610500, Chengdu, China;

关键词: Mesenchymal stem cells;    Placenta;    Severe acute pancreatitis;    Macrophage polarization;    TSG-6;   

DOI  :  10.1186/s13287-021-02411-9

来源: Springer

【 摘 要 】

BackgroundMesenchymal stem cells (MSCs) hold promising potential to treat systemic inflammatory diseases including severe acute pancreatitis (SAP). In our previous study, placental chorionic plate-derived MSCs (CP-MSCs) were found to possess superior immunoregulatory capability. However, the therapeutic efficacy of CP-MSCs on SAP and their underlying mechanism remain unclear.MethodsThe survival and colonization of exogenous CP-MSCs were observed by bioluminescence imaging and CM-Dil labeling in rodent animal models of SAP. The therapeutic efficacy of CP-MSCs on SAP rats was evaluated by pathology scores, the levels of pancreatitis biomarkers as well as the levels of inflammatory factors in the pancreas and serum. The potential protective mechanism of CP-MSCs in SAP rats was explored by selectively depleting M1 or M2 phenotype macrophages and knocking down the expression of TSG-6.ResultsExogenous CP-MSCs could survive and colonize in the injured tissue of SAP such as the lung, pancreas, intestine, and liver. Meanwhile, we found that CP-MSCs alleviated pancreatic injury and systemic inflammation by inducing macrophages to polarize from M1 to M2 in SAP rats. Furthermore, our data suggested that CP-MSCs induced M2 polarization of macrophages by secreting TSG-6, and TSG-6 played a vital role in alleviating pancreatic injury and systemic inflammation in SAP rats. Notably, we found that a high inflammation environment could stimulate CP-MSCs to secrete TSG-6.ConclusionExogenous CP-MSCs tended to colonize in the injured tissue and reduced pancreatic injury and systemic inflammation in SAP rats through inducing M2 polarization of macrophages by secreting TSG-6. Our study provides a new treatment strategy for SAP and initially explains the potential protective mechanism of CP-MSCs on SAP rats.

【 授权许可】

CC BY