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Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting necroptosis in rats

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Abstract

The treatment and prognosis for severe acute pancreatitis (SAP) is currently unsatisfactory showing a high incidence of morbidity and mortality. Here, we investigated the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on SAP in rats and explored the possible mechanisms. The common bile duct of each model rat was occluded at the liver hilum, and the induction of SAP was achieved by retrograde perfusion of 3% sodium taurocholate (NaT). Prepared BMSCs were intravenously injected via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreas, and induced by TNF-α. In the present study, we found that necroptosis was activated in NaT-induced acute-necrotized pancreatitis, and transplanted BMSCs could inhibit necroptosis, repair pancreatic injury, and reduce systemic inflammatory response. In addition, necrostatin-1 (Nec-1), as the inhibitor of receptor-interacting protein kinase 1 (RIPK1), could also reduce SAP to some extent. Besides, we detected that BMSCs could also promote regeneration of damaged pancreatic tissues. Furthermore, in vitro, we also investigated that BMSCs could suppress TNF-α-induced necroptosis and improve the viability of PACs. In addition, Nec-1 and knockdown of receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain-like protein (MLKL) could also inhibit necrosis of PACs induced by TNF-α. BMSCs ameliorated SAP and reduced injury of PACs by suppressing the activation of the necroptosis signaling pathway.

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Acknowledgements

The present study was supported by research grants from the National Natural Science Foundation of China (Grant No. 81670582), the College Natural Science Foundation of Anhui Province (Grant No. KJ2017A271), and the Talent Introduction Fund of Yijishan Hospital of Wannan Medical School (Grant No. YR201601).

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  1. Guodong Song, Zhilong Ma and Dalu Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Shanghai Tenth People’s Hospital, Affiliated to Tongji University School of Medicine, Yanchang Road 301, Shanghai, 200072, China

    Guodong Song, Zhilong Ma, Hongbo Meng, Bo Zhou & Zhenshun Song

  2. Shanghai Clinical Medical College of Anhui Medical University, Hefei, 230032, Anhui, China

    Dalu Liu

  3. Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China

    Jia Zhou

  4. Department of Hepatobiliary Surgery, Yijishan Hospital, Wannan Medical College, 2 West Zheshan Road, Anhui, 241001, China

    Daohai Qian

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  1. Guodong Song
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Song, G., Ma, Z., Liu, D. et al. Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting necroptosis in rats. Mol Cell Biochem 459, 7–19 (2019). https://doi.org/10.1007/s11010-019-03546-3

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