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

Qian D, Gong J, He Z, Hua J, Lin S, Xu C, Meng H, Song Z - Stem Cells Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

qRT-PCR or western-blot assays are showing that the expressions of ANG-1, VEGF, HGF, TGF-β, and CD31 in pancreatic tissue were significantly higher in SAP+BMSCs group. ((a), (c), and (d)) The expression of ANG-1 was investigated higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. ((b), (c), and (e)) There was a significant higher expression of VEGF in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups at posttransplant days 1 and 4, with a subsequent decrease at day 7. ((f)–(h)) The mRNA level of HGF, TGF-β, and CD31 was significantly higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. Data are expressed as mean ± SD (#P > 0.05 for sham versus NC, *P < 0.05 and **P < 0.01 for SAP+BMSCs versus NC, †P < 0.05, ††P < 0.01, and †††P < 0.001 for SAP+BMSCs versus SAP,  $ P < 0.05,  $$ P < 0.01, and  $$$ P < 0.001 for SAP+BMSCs versus SAP+anti-CXCR4 BMSCs at each corresponding time point) (NC, normal control, ANG-1, angiopoietin-1, VEGF, vascular endothelial growth factor, SAP, severe acute pancreatitis, and BMSCs, bone marrow-derived mesenchymal stem cells).
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fig7: qRT-PCR or western-blot assays are showing that the expressions of ANG-1, VEGF, HGF, TGF-β, and CD31 in pancreatic tissue were significantly higher in SAP+BMSCs group. ((a), (c), and (d)) The expression of ANG-1 was investigated higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. ((b), (c), and (e)) There was a significant higher expression of VEGF in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups at posttransplant days 1 and 4, with a subsequent decrease at day 7. ((f)–(h)) The mRNA level of HGF, TGF-β, and CD31 was significantly higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. Data are expressed as mean ± SD (#P > 0.05 for sham versus NC, *P < 0.05 and **P < 0.01 for SAP+BMSCs versus NC, †P < 0.05, ††P < 0.01, and †††P < 0.001 for SAP+BMSCs versus SAP,  $ P < 0.05,  $$ P < 0.01, and  $$$ P < 0.001 for SAP+BMSCs versus SAP+anti-CXCR4 BMSCs at each corresponding time point) (NC, normal control, ANG-1, angiopoietin-1, VEGF, vascular endothelial growth factor, SAP, severe acute pancreatitis, and BMSCs, bone marrow-derived mesenchymal stem cells).

Mentions: VEGF expression in injured pancreatic tissues was measured with qRT-PCR and immunoblotting. VEGF expression was higher in the SAP+BMSCS group than in the normal control, SAP and SAP+anti-CXCR4 BMSCs groups on postoperative days 1 and 4 but had decreased on postoperative day 7 (Figures 7(b), 7(c), and 7(e)). The expression of ANG-1 was detected with qRT-PCR and immunoblotting and its expression was higher in the SAP+BMSCS group than in the normal control, SAP, and SAP+anti-CXCR4 BMSCs groups (Figures 7(a), 7(c), and 7(d)). The mRNA levels of HGF and TGF-β were also detected with qRT-PCR and were significantly higher in the SAP+BMSCs group than in the normal, SAP, and SAP+anti-CXCR4 BMSCs groups (Figures 7(f) and 7(g)).


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

Qian D, Gong J, He Z, Hua J, Lin S, Xu C, Meng H, Song Z - Stem Cells Int (2015)

qRT-PCR or western-blot assays are showing that the expressions of ANG-1, VEGF, HGF, TGF-β, and CD31 in pancreatic tissue were significantly higher in SAP+BMSCs group. ((a), (c), and (d)) The expression of ANG-1 was investigated higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. ((b), (c), and (e)) There was a significant higher expression of VEGF in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups at posttransplant days 1 and 4, with a subsequent decrease at day 7. ((f)–(h)) The mRNA level of HGF, TGF-β, and CD31 was significantly higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. Data are expressed as mean ± SD (#P > 0.05 for sham versus NC, *P < 0.05 and **P < 0.01 for SAP+BMSCs versus NC, †P < 0.05, ††P < 0.01, and †††P < 0.001 for SAP+BMSCs versus SAP,  $ P < 0.05,  $$ P < 0.01, and  $$$ P < 0.001 for SAP+BMSCs versus SAP+anti-CXCR4 BMSCs at each corresponding time point) (NC, normal control, ANG-1, angiopoietin-1, VEGF, vascular endothelial growth factor, SAP, severe acute pancreatitis, and BMSCs, bone marrow-derived mesenchymal stem cells).
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fig7: qRT-PCR or western-blot assays are showing that the expressions of ANG-1, VEGF, HGF, TGF-β, and CD31 in pancreatic tissue were significantly higher in SAP+BMSCs group. ((a), (c), and (d)) The expression of ANG-1 was investigated higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. ((b), (c), and (e)) There was a significant higher expression of VEGF in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups at posttransplant days 1 and 4, with a subsequent decrease at day 7. ((f)–(h)) The mRNA level of HGF, TGF-β, and CD31 was significantly higher in SAP+BMSCs group than in normal, SAP, and SAP+anti-CXCR4 BMSCs groups. Data are expressed as mean ± SD (#P > 0.05 for sham versus NC, *P < 0.05 and **P < 0.01 for SAP+BMSCs versus NC, †P < 0.05, ††P < 0.01, and †††P < 0.001 for SAP+BMSCs versus SAP,  $ P < 0.05,  $$ P < 0.01, and  $$$ P < 0.001 for SAP+BMSCs versus SAP+anti-CXCR4 BMSCs at each corresponding time point) (NC, normal control, ANG-1, angiopoietin-1, VEGF, vascular endothelial growth factor, SAP, severe acute pancreatitis, and BMSCs, bone marrow-derived mesenchymal stem cells).
Mentions: VEGF expression in injured pancreatic tissues was measured with qRT-PCR and immunoblotting. VEGF expression was higher in the SAP+BMSCS group than in the normal control, SAP and SAP+anti-CXCR4 BMSCs groups on postoperative days 1 and 4 but had decreased on postoperative day 7 (Figures 7(b), 7(c), and 7(e)). The expression of ANG-1 was detected with qRT-PCR and immunoblotting and its expression was higher in the SAP+BMSCS group than in the normal control, SAP, and SAP+anti-CXCR4 BMSCs groups (Figures 7(a), 7(c), and 7(d)). The mRNA levels of HGF and TGF-β were also detected with qRT-PCR and were significantly higher in the SAP+BMSCs group than in the normal, SAP, and SAP+anti-CXCR4 BMSCs groups (Figures 7(f) and 7(g)).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus