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

Autor: Ying Zhu, Bing-Wei Liu, Ming-Li Zhu, Xiao-Kang Zeng, Wei-Ying Dai, Shaosong Xi, Jing Yang, Xian-Fu Ke, Wei Hu, Jun Su, Huapeng Lin
Rok vydání: 2019
Předmět:
0301 basic medicine
Angiogenesis
Endothelial cells
Neovascularization
Physiologic
Apoptosis
RM1-950
Pharmacology
Mesenchymal Stem Cell Transplantation
Umbilical cord
Models
Biological
Umbilical vein
Umbilical Cord
03 medical and health sciences
0302 clinical medicine
Paracrine Communication
Human Umbilical Vein Endothelial Cells
Medicine
Animals
Humans
Pancreas
Tube formation
business.industry
Angiotensin II
Mesenchymal stem cell
hUC-MSCs
Mesenchymal Stem Cells
General Medicine
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Rats
Endothelial stem cell
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Pancreatitis
030220 oncology & carcinogenesis
Culture Media
Conditioned
Acute Disease
cardiovascular system
Angiotensin-II
Therapeutics. Pharmacology
business
SAP
Zdroj: Biomedicine & Pharmacotherapy, Vol 117, Iss, Pp-(2019)
ISSN: 1950-6007
Popis: 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.
Databáze: OpenAIRE
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