Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats

Acute pancreatitis (AP), a common acute abdominal disease, 10%–20% of which can evolve into severe acute pancreatitis (SAP), is of significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to have a potential therapeutic role on SAP, but the specific...

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Main Authors: Daohai Qian, Jian Gong, Zhigang He, Jie Hua, Shengping Lin, Chenglei Xu, Hongbo Meng, Zhenshun Song
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/306836
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author Daohai Qian
Jian Gong
Zhigang He
Jie Hua
Shengping Lin
Chenglei Xu
Hongbo Meng
Zhenshun Song
author_facet Daohai Qian
Jian Gong
Zhigang He
Jie Hua
Shengping Lin
Chenglei Xu
Hongbo Meng
Zhenshun Song
author_sort Daohai Qian
collection DOAJ
description Acute pancreatitis (AP), a common acute abdominal disease, 10%–20% of which can evolve into severe acute pancreatitis (SAP), is of significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to have a potential therapeutic role on SAP, but the specific mechanism is unclear. Therefore, we conducted this experiment to shed light on the probable mechanism. We validated that SDF-1α significantly stimulated the expressions of VEGF, ANG-1, HGF, TGF-β, and CXCR4 in BMSCs, which were inhibited by its receptor agonist, AMD3100. The capacities of proliferation, migration, and repair of human umbilical vein endothelial cells were enhanced by BMSCs supernatant. Meanwhile, BMSCs supernatant could also promote angiogenesis, especially after the stimulation with SDF-1α. In vivo, the migration of BMSCs was regulated by SDF-1α/CXCR4 axis. Moreover, transplanted BMSCs could significantly alleviate SAP, reduce the systematic inflammation (TNF-α↓, IL-1β↓, IL-6↓, IL-4↑, IL-10↑, and TGF-β↑), and promote tissue repair and angiogenesis (VEGF↑, ANG-1↑, HGF↑, TGF-β↑, and CD31↑), compared with the SAP and anti-CXCR4 groups. Taken together, the results showed that BMSCs ameliorated SAP and the SDF-1α/CXCR4 axis was involved in the repair and regeneration process.
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spelling doaj-art-7a0cbbd0ceb34fe98d4ff910748e31692025-02-03T06:12:11ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/306836306836Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in RatsDaohai Qian0Jian Gong1Zhigang He2Jie Hua3Shengping Lin4Chenglei Xu5Hongbo Meng6Zhenshun Song7Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaDepartment of General Surgery, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, ChinaAcute pancreatitis (AP), a common acute abdominal disease, 10%–20% of which can evolve into severe acute pancreatitis (SAP), is of significant morbidity and mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to have a potential therapeutic role on SAP, but the specific mechanism is unclear. Therefore, we conducted this experiment to shed light on the probable mechanism. We validated that SDF-1α significantly stimulated the expressions of VEGF, ANG-1, HGF, TGF-β, and CXCR4 in BMSCs, which were inhibited by its receptor agonist, AMD3100. The capacities of proliferation, migration, and repair of human umbilical vein endothelial cells were enhanced by BMSCs supernatant. Meanwhile, BMSCs supernatant could also promote angiogenesis, especially after the stimulation with SDF-1α. In vivo, the migration of BMSCs was regulated by SDF-1α/CXCR4 axis. Moreover, transplanted BMSCs could significantly alleviate SAP, reduce the systematic inflammation (TNF-α↓, IL-1β↓, IL-6↓, IL-4↑, IL-10↑, and TGF-β↑), and promote tissue repair and angiogenesis (VEGF↑, ANG-1↑, HGF↑, TGF-β↑, and CD31↑), compared with the SAP and anti-CXCR4 groups. Taken together, the results showed that BMSCs ameliorated SAP and the SDF-1α/CXCR4 axis was involved in the repair and regeneration process.http://dx.doi.org/10.1155/2015/306836
spellingShingle Daohai Qian
Jian Gong
Zhigang He
Jie Hua
Shengping Lin
Chenglei Xu
Hongbo Meng
Zhenshun Song
Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
Stem Cells International
title Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
title_full Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
title_fullStr Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
title_full_unstemmed Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
title_short Bone Marrow-Derived Mesenchymal Stem Cells Repair Necrotic Pancreatic Tissue and Promote Angiogenesis by Secreting Cellular Growth Factors Involved in the SDF-1α/CXCR4 Axis in Rats
title_sort bone marrow derived mesenchymal stem cells repair necrotic pancreatic tissue and promote angiogenesis by secreting cellular growth factors involved in the sdf 1α cxcr4 axis in rats
url http://dx.doi.org/10.1155/2015/306836
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