Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6
| Autor: | Hongbo Meng, Zhenshun Song, Daohai Qian, Jian Gong, Ge Wei, Shengping Lin, Jie Hua, Bo Zhou, Tingsong Yang, Chenglei Xu, Zhigang He |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Inflammasomes Biology medicine.disease_cause Mesenchymal Stem Cell Transplantation Article Immunomodulation 03 medical and health sciences Mice NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans Secretion Receptor Gene knockdown Multidisciplinary Tumor Necrosis Factor-alpha Mesenchymal stem cell NF-kappa B Inflammasome medicine.disease equipment and supplies Oxidative Stress 030104 developmental biology medicine.anatomical_structure Hyaluronan Receptors Pancreatitis Immunology Cancer research Acute pancreatitis Administration Intravenous Pancreas Cell Adhesion Molecules Oxidative stress medicine.drug Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep38438 |
| Popis: | The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF-κB signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|