PMID- 30600195 OWN - NLM STAT- MEDLINE DCOM- 20200224 LR - 20200224 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 21 IP - 2 DP - 2019 Feb TI - Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatory effects. PG - 162-174 LID - S1465-3249(18)30705-9 [pii] LID - 10.1016/j.jcyt.2018.11.013 [doi] AB - BACKGROUND AND AIMS: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1). METHODS: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated. RESULTS: Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP. CONCLUSIONS: BMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and anti-oxidant effects, reduce apoptosis and promote angiogenesis. CI - Copyright (c) 2018 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved. FAU - Ma, Zhilong AU - Ma Z AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Song, Guodong AU - Song G AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Zhao, Dongbo AU - Zhao D AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Clinical Medical College of Nanjing Medical University, Nanjing, China. FAU - Liu, Dalu AU - Liu D AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai Clinical Medical College of Anhui Medical University, Hefei, China. FAU - Liu, Xiaolei AU - Liu X AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Dai, Yuxiang AU - Dai Y AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - He, Zhigang AU - He Z AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Qian, Daohai AU - Qian D AD - Department of Hepatobiliary Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, China. FAU - Gong, Jian AU - Gong J AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Meng, Hongbo AU - Meng H AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Zhou, B O AU - Zhou BO AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Yang, Tingsong AU - Yang T AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: zs_song@hotmail.com. FAU - Song, Zhenshun AU - Song Z AD - Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: tingsong.yang@tongji.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181229 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Reactive Oxygen Species) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.2.1.- (Amylases) SB - IM MH - Amylases/blood MH - Animals MH - Apoptosis MH - Catalase/metabolism MH - Heme Oxygenase (Decyclizing)/*metabolism MH - Inflammation/metabolism MH - Male MH - Malondialdehyde/metabolism MH - *Mesenchymal Stem Cell Transplantation MH - Neovascularization, Physiologic MH - Oxidative Stress/*physiology MH - Pancreatitis/chemically induced/*metabolism/*therapy MH - Peroxidase/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - heme oxygenase-1 OT - inflammatory OT - mesenchymal stromal cells OT - oxidative stress OT - severe acute pancreatitis EDAT- 2019/01/03 06:00 MHDA- 2020/02/25 06:00 CRDT- 2019/01/03 06:00 PHST- 2018/06/13 00:00 [received] PHST- 2018/11/09 00:00 [revised] PHST- 2018/11/20 00:00 [accepted] PHST- 2019/01/03 06:00 [pubmed] PHST- 2020/02/25 06:00 [medline] PHST- 2019/01/03 06:00 [entrez] AID - S1465-3249(18)30705-9 [pii] AID - 10.1016/j.jcyt.2018.11.013 [doi] PST - ppublish SO - Cytotherapy. 2019 Feb;21(2):162-174. doi: 10.1016/j.jcyt.2018.11.013. Epub 2018 Dec 29.