Journal
CYTOTHERAPY
Volume 21, Issue 2, Pages 162-174Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2018.11.013
Keywords
heme oxygenase-1; inflammatory; mesenchymal stromal cells; oxidative stress; severe acute pancreatitis
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Funding
- National Natural Science Foundation of China [81670582]
- Talent Introduction Fund of Yijishan Hospital of Wannan Medical School [YR201601]
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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 antioxidant effects, reduce apoptosis and promote angiogenesis.
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