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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

Basic fibroblast growth factor (bFGF) promotes mesenchymal stem cells (MSCs) migration and differentiation into a cardiomyocyte phenotype in vitro. (A) MSCs were cultured under normoxic and hypoxic conditions with 50 ng/mL bFGF, 20 ng/mL vascular endothelial growth factor (VEGF), 2 ng/mL insulin-like growth factor (IGF-1), or control medium. Under hypoxic conditions, the number of migrated cells increased when incubated with VEGF, IGF-1, and bFGF. (B) Myotube-like structures were observed in differentiated MSCs (dMSCs). (C) Cotreatment with bFGF induced MSCs differentiation into a cardiomyocyte phenotype, as indicated by increased cardiac troponin I positive (TnI+) cells. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI). Scale bars: 200μm (A); 100μm (B and C). Histograms represent mean±SEM. A: *p<0.05 vs normoxia; †p<0.05 vs control. All with 2-way ANOVA. C: *p<0.05 vs control, unpaired Student t test.
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Figure 2: Basic fibroblast growth factor (bFGF) promotes mesenchymal stem cells (MSCs) migration and differentiation into a cardiomyocyte phenotype in vitro. (A) MSCs were cultured under normoxic and hypoxic conditions with 50 ng/mL bFGF, 20 ng/mL vascular endothelial growth factor (VEGF), 2 ng/mL insulin-like growth factor (IGF-1), or control medium. Under hypoxic conditions, the number of migrated cells increased when incubated with VEGF, IGF-1, and bFGF. (B) Myotube-like structures were observed in differentiated MSCs (dMSCs). (C) Cotreatment with bFGF induced MSCs differentiation into a cardiomyocyte phenotype, as indicated by increased cardiac troponin I positive (TnI+) cells. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI). Scale bars: 200μm (A); 100μm (B and C). Histograms represent mean±SEM. A: *p<0.05 vs normoxia; †p<0.05 vs control. All with 2-way ANOVA. C: *p<0.05 vs control, unpaired Student t test.

Mentions: The number of migrated cells was significantly greater when incubated under hypoxic versus normoxic conditions in control (p=0.006), IGF-1 (p=0.002), and bFGF (p<0.001) groups (Figure 2A). During hypoxia, MSCs exhibited increased migratory ability when cultured with VEGF, IGF-1, and bFGF (all p<0.001 vs control).


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)

Basic fibroblast growth factor (bFGF) promotes mesenchymal stem cells (MSCs) migration and differentiation into a cardiomyocyte phenotype in vitro. (A) MSCs were cultured under normoxic and hypoxic conditions with 50 ng/mL bFGF, 20 ng/mL vascular endothelial growth factor (VEGF), 2 ng/mL insulin-like growth factor (IGF-1), or control medium. Under hypoxic conditions, the number of migrated cells increased when incubated with VEGF, IGF-1, and bFGF. (B) Myotube-like structures were observed in differentiated MSCs (dMSCs). (C) Cotreatment with bFGF induced MSCs differentiation into a cardiomyocyte phenotype, as indicated by increased cardiac troponin I positive (TnI+) cells. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI). Scale bars: 200μm (A); 100μm (B and C). Histograms represent mean±SEM. A: *p<0.05 vs normoxia; †p<0.05 vs control. All with 2-way ANOVA. C: *p<0.05 vs control, unpaired Student t test.
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Related In: Results  -  Collection

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Figure 2: Basic fibroblast growth factor (bFGF) promotes mesenchymal stem cells (MSCs) migration and differentiation into a cardiomyocyte phenotype in vitro. (A) MSCs were cultured under normoxic and hypoxic conditions with 50 ng/mL bFGF, 20 ng/mL vascular endothelial growth factor (VEGF), 2 ng/mL insulin-like growth factor (IGF-1), or control medium. Under hypoxic conditions, the number of migrated cells increased when incubated with VEGF, IGF-1, and bFGF. (B) Myotube-like structures were observed in differentiated MSCs (dMSCs). (C) Cotreatment with bFGF induced MSCs differentiation into a cardiomyocyte phenotype, as indicated by increased cardiac troponin I positive (TnI+) cells. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI). Scale bars: 200μm (A); 100μm (B and C). Histograms represent mean±SEM. A: *p<0.05 vs normoxia; †p<0.05 vs control. All with 2-way ANOVA. C: *p<0.05 vs control, unpaired Student t test.
Mentions: The number of migrated cells was significantly greater when incubated under hypoxic versus normoxic conditions in control (p=0.006), IGF-1 (p=0.002), and bFGF (p<0.001) groups (Figure 2A). During hypoxia, MSCs exhibited increased migratory ability when cultured with VEGF, IGF-1, and bFGF (all p<0.001 vs control).

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