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Biomed Pharmacother. 2019 Jun 5;117:109052. doi: 10.1016/j.biopha.2019.109052. [Epub ahead of print]

Human umbilical cord mesenchymal stem cells pretreated with Angiotensin-II attenuate pancreas injury of rats with severe acute pancreatitis.

Author information

1
Department of Intensive Care Unit, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 261 Huansha Road, Hangzhou 310006, People's Republic of China.
2
Zhejiang Academy Of Medical Science, 182 Tianmushan Road, Hangzhou 310000, People's Republic of China.
3
Department of Intensive Care Unit, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 261 Huansha Road, Hangzhou 310006, People's Republic of China. Electronic address: 13575721596@163.com.

Abstract

Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo.

METHODS:

In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12 h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated.

RESULTS:

We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM.

CONCLUSION:

Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.

KEYWORDS:

Angiogenesis; Angiotensin-II; Endothelial cells; SAP; hUC-MSCs

PMID:
31176170
DOI:
10.1016/j.biopha.2019.109052
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