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Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction.

Wang X, Zhen L, Miao H, Sun Q, Yang Y, Que B, Lopes Lao EP, Wu X, Ren H, Shi S, Lau WB, Ma X, Ma C, Nie S - Theranostics (2015)

Bottom Line: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype.Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001).Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).

View Article: PubMed Central - PubMed

Affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;

ABSTRACT

Aim: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model.

Methods and results: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).

Conclusions: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.

No MeSH data available.


Related in: MedlinePlus

Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) induces neovascularization and inhibits apoptosis. Representative micrographs demonstrated formation of (A) new capillaries and (B) arterioles in the infarct border region after treatment. Quantitative analysis indicated markedly greater (A) capillary density (evidenced by factor VIII-related antigen [FVIII] staining) and (B) arteriole density (evidenced by α-smooth muscle actin [α-SMA] staining) in the bFGF+MSCs group. (C) Representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the border region of the infarct myocardium. Cell nuclei were counterstained with 4,6-diamidino-2-phenylindole (DAPI). The proportion of TUNEL+ cells was significantly decreased in the bFGF+MSCs group. Scale bars: 50μm (A); 100μm (B); 20μm (C). Histograms represent mean±SEM. *p<0.05 vs saline; †p<0.05 vs bFGF; ‡p<0.05 vs MSCs. All with 1-way ANOVA by Tukey post hoc test.
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Figure 5: Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) induces neovascularization and inhibits apoptosis. Representative micrographs demonstrated formation of (A) new capillaries and (B) arterioles in the infarct border region after treatment. Quantitative analysis indicated markedly greater (A) capillary density (evidenced by factor VIII-related antigen [FVIII] staining) and (B) arteriole density (evidenced by α-smooth muscle actin [α-SMA] staining) in the bFGF+MSCs group. (C) Representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the border region of the infarct myocardium. Cell nuclei were counterstained with 4,6-diamidino-2-phenylindole (DAPI). The proportion of TUNEL+ cells was significantly decreased in the bFGF+MSCs group. Scale bars: 50μm (A); 100μm (B); 20μm (C). Histograms represent mean±SEM. *p<0.05 vs saline; †p<0.05 vs bFGF; ‡p<0.05 vs MSCs. All with 1-way ANOVA by Tukey post hoc test.

Mentions: Capillary and arteriole density was determined (respectively by FVIII and α-SMA staining) in the infarct border zones. The number of FVIII+ cells was markedly greater in the bFGF+MSCs group (97.1±8.3/mm2) compared to the saline (40.0±5.3/mm2; p<0.001), bFGF (60.0±5.2/mm2; p<0.01), and MSCs (54.3±5.4/mm2; p<0.001) groups (Figure 5A). The arteriolar density was significantly greater in the bFGF+MSCs group (35.7±3.2/mm2) compared to the saline (15.0±2.4/mm2; p<0.05) and MSCs (23.6±2.4/mm2; p<0.05) groups (Figure 5B).


Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction.

Wang X, Zhen L, Miao H, Sun Q, Yang Y, Que B, Lopes Lao EP, Wu X, Ren H, Shi S, Lau WB, Ma X, Ma C, Nie S - Theranostics (2015)

Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) induces neovascularization and inhibits apoptosis. Representative micrographs demonstrated formation of (A) new capillaries and (B) arterioles in the infarct border region after treatment. Quantitative analysis indicated markedly greater (A) capillary density (evidenced by factor VIII-related antigen [FVIII] staining) and (B) arteriole density (evidenced by α-smooth muscle actin [α-SMA] staining) in the bFGF+MSCs group. (C) Representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the border region of the infarct myocardium. Cell nuclei were counterstained with 4,6-diamidino-2-phenylindole (DAPI). The proportion of TUNEL+ cells was significantly decreased in the bFGF+MSCs group. Scale bars: 50μm (A); 100μm (B); 20μm (C). Histograms represent mean±SEM. *p<0.05 vs saline; †p<0.05 vs bFGF; ‡p<0.05 vs MSCs. All with 1-way ANOVA by Tukey post hoc test.
© Copyright Policy
Related In: Results  -  Collection

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Figure 5: Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) induces neovascularization and inhibits apoptosis. Representative micrographs demonstrated formation of (A) new capillaries and (B) arterioles in the infarct border region after treatment. Quantitative analysis indicated markedly greater (A) capillary density (evidenced by factor VIII-related antigen [FVIII] staining) and (B) arteriole density (evidenced by α-smooth muscle actin [α-SMA] staining) in the bFGF+MSCs group. (C) Representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the border region of the infarct myocardium. Cell nuclei were counterstained with 4,6-diamidino-2-phenylindole (DAPI). The proportion of TUNEL+ cells was significantly decreased in the bFGF+MSCs group. Scale bars: 50μm (A); 100μm (B); 20μm (C). Histograms represent mean±SEM. *p<0.05 vs saline; †p<0.05 vs bFGF; ‡p<0.05 vs MSCs. All with 1-way ANOVA by Tukey post hoc test.
Mentions: Capillary and arteriole density was determined (respectively by FVIII and α-SMA staining) in the infarct border zones. The number of FVIII+ cells was markedly greater in the bFGF+MSCs group (97.1±8.3/mm2) compared to the saline (40.0±5.3/mm2; p<0.001), bFGF (60.0±5.2/mm2; p<0.01), and MSCs (54.3±5.4/mm2; p<0.001) groups (Figure 5A). The arteriolar density was significantly greater in the bFGF+MSCs group (35.7±3.2/mm2) compared to the saline (15.0±2.4/mm2; p<0.05) and MSCs (23.6±2.4/mm2; p<0.05) groups (Figure 5B).

Bottom Line: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype.Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001).Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).

View Article: PubMed Central - PubMed

Affiliation: 1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China;

ABSTRACT

Aim: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model.

Methods and results: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05).

Conclusions: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.

No MeSH data available.


Related in: MedlinePlus