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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

There is similarity in the proliferation and CXCR4 expression between unlabeled and SPION-labeled BMSCs ([Fe3+] = 25 g/mL). (a) The Prussian blue staining shows that BMSCs were labeled by SPION successfully. (b) The MTT tests are showing that the growth activity of SPION-labeled BMSCs ([Fe3+] = 25 g/mL) slowed slightly compared with that of the unlabeled BMSCs, which was also significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 g/mL). Data are expressed as mean ± SD (&&P < 0.01 and &&&P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 100 g/mL),  $$ P < 0.01 and  $$$ P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 75 g/mL), and †P < 0.05 and †††P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 50 g/mL) at each corresponding time point). ((c)-(d)) CXCR4 expression was detected by immunofluorescence and western blotting and similar between unlabeled and SPION-labeled BMSCs (P > 0.05). (SPION, superparamagnetic iron oxide nanoparticles, BMSCs, bone marrow-derived mesenchymal stem cells).
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fig3: There is similarity in the proliferation and CXCR4 expression between unlabeled and SPION-labeled BMSCs ([Fe3+] = 25 g/mL). (a) The Prussian blue staining shows that BMSCs were labeled by SPION successfully. (b) The MTT tests are showing that the growth activity of SPION-labeled BMSCs ([Fe3+] = 25 g/mL) slowed slightly compared with that of the unlabeled BMSCs, which was also significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 g/mL). Data are expressed as mean ± SD (&&P < 0.01 and &&&P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 100 g/mL),  $$ P < 0.01 and  $$$ P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 75 g/mL), and †P < 0.05 and †††P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 50 g/mL) at each corresponding time point). ((c)-(d)) CXCR4 expression was detected by immunofluorescence and western blotting and similar between unlabeled and SPION-labeled BMSCs (P > 0.05). (SPION, superparamagnetic iron oxide nanoparticles, BMSCs, bone marrow-derived mesenchymal stem cells).

Mentions: More than 95% of BMSCs were successfully labeled with SPION ([Fe3+] = 25 μg/mL) (Figure 3(a)). The growth activity of SPION-labeled BMSCs ([Fe3+] = 25 μg/mL) was similar to unlabeled BMSCs, which was significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 μg/mL) (Figure 3(b)). CXCR4 expression was observed with confocal microscopy and similar in both the BMSCs and SPION-labeled BMSCs (Figures 3(c)–3(e)).


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)

There is similarity in the proliferation and CXCR4 expression between unlabeled and SPION-labeled BMSCs ([Fe3+] = 25 g/mL). (a) The Prussian blue staining shows that BMSCs were labeled by SPION successfully. (b) The MTT tests are showing that the growth activity of SPION-labeled BMSCs ([Fe3+] = 25 g/mL) slowed slightly compared with that of the unlabeled BMSCs, which was also significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 g/mL). Data are expressed as mean ± SD (&&P < 0.01 and &&&P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 100 g/mL),  $$ P < 0.01 and  $$$ P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 75 g/mL), and †P < 0.05 and †††P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 50 g/mL) at each corresponding time point). ((c)-(d)) CXCR4 expression was detected by immunofluorescence and western blotting and similar between unlabeled and SPION-labeled BMSCs (P > 0.05). (SPION, superparamagnetic iron oxide nanoparticles, BMSCs, bone marrow-derived mesenchymal stem cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: There is similarity in the proliferation and CXCR4 expression between unlabeled and SPION-labeled BMSCs ([Fe3+] = 25 g/mL). (a) The Prussian blue staining shows that BMSCs were labeled by SPION successfully. (b) The MTT tests are showing that the growth activity of SPION-labeled BMSCs ([Fe3+] = 25 g/mL) slowed slightly compared with that of the unlabeled BMSCs, which was also significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 g/mL). Data are expressed as mean ± SD (&&P < 0.01 and &&&P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 100 g/mL),  $$ P < 0.01 and  $$$ P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 75 g/mL), and †P < 0.05 and †††P < 0.001 for normal control versus SPION-labeled BMSCS ([Fe3+] = 50 g/mL) at each corresponding time point). ((c)-(d)) CXCR4 expression was detected by immunofluorescence and western blotting and similar between unlabeled and SPION-labeled BMSCs (P > 0.05). (SPION, superparamagnetic iron oxide nanoparticles, BMSCs, bone marrow-derived mesenchymal stem cells).
Mentions: More than 95% of BMSCs were successfully labeled with SPION ([Fe3+] = 25 μg/mL) (Figure 3(a)). The growth activity of SPION-labeled BMSCs ([Fe3+] = 25 μg/mL) was similar to unlabeled BMSCs, which was significantly stronger than that of other SPION-labeled BMSCs ([Fe3+] = 50, 75, or 100 μg/mL) (Figure 3(b)). CXCR4 expression was observed with confocal microscopy and similar in both the BMSCs and SPION-labeled BMSCs (Figures 3(c)–3(e)).

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