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

Qilin Huang,Ruohong Liu,Xiumei Cheng,Shuai Li,Shuxu Yang,Chen Luo,Yi Yang,Bing Wang,Hongyu Sun,Lijun Tang,Yi Wen,Xiaohui Yuan

doi:10.1186/s13287-021-02411-9

Qilin Huang, Ruohong Liu + Show 10 more

Open Access

https://doi.org/10.1186/s13287-021-02411-9

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Abstract

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.

Highlights

Severe acute pancreatitis (SAP) is a deadly inflammatory disease caused by local pancreatic lesions, and excessive hyperinflammation caused by immune imbalance is an important cause of systemic inflammatory response syndrome (SIRS) and secondary organ dysfunction [1, 2]
Our study provides a new treatment strategy for severe acute pancreatitis (SAP) and initially explains the potential protective mechanism of chorionic plate-derived Mesenchymal stem cells (MSCs) (CP-MSCs) on SAP rats
The important findings of this study are as follows: (i) Exogenous CP-MSCs can survive in the hyperinflammatory environment of SAP and tend to colonize the injured tissue, such as the pancreas, lung, liver, and intestine; (ii) CP-MSCs alleviate pancreatic injury and systemic inflammatory by inducing macrophage polarization from M1 to M2 in SAP rats; (iii) CP-MSCs secrete more tumor necrosis factor-α-induced gene/protein 6 (TSG-6) in the inflammatory environment of SAP, thereby inducing macrophages to polarize from M1 to M2; (iv) TSG-6 secreted by CP-MSCs play a vital role in alleviating pancreatic injury and systemic inflammation in SAP rats

Summary

Introduction

Severe acute pancreatitis (SAP) is a deadly inflammatory disease caused by local pancreatic lesions, and excessive hyperinflammation caused by immune imbalance is an important cause of systemic inflammatory response syndrome (SIRS) and secondary organ dysfunction [1, 2]. Mesenchymal stem cells (MSCs) retain promising potential in the treatment of various inflammatory and immune diseases due to their remarkable anti-inflammatory and immunoregulatory capabilities [4,5,6,7]. Some studies have confirmed that placentalderived MSCs (P-MSCs) have the advantages of rich tissue sources, easy noninvasive access, and few ethical restrictions, and possess stronger immunoregulation and proliferation capacity. Consistent with this, a study showed that CD106+ MSCs possessed stronger proliferation and immunoregulation capabilities than CD106− MSCs [14]. Mesenchymal stem cells (MSCs) hold promising potential to treat systemic inflammatory diseases including severe acute pancreatitis (SAP). Placental chorionic plate-derived MSCs (CP-MSCs) were found to possess superior immunoregulatory capability. The therapeutic efficacy of CP-MSCs on SAP and their underlying mechanism remain unclear

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