Limits...
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) increases infarct wall thickness and reduces myocardial fibrosis. (A) Post-mortem morphometry revealed midmural scars in the left ventricular wall. Coronary venous infusion of bFGFs+MSCs increased infarct wall thickness compared to other groups. The percentage of infarct wall thickness to septal wall thickness was greatest in the bFGF+MSCs group. (B) Masson's trichrome staining showed decreased collagen content in the MSCs and bFGF+MSCs groups both in the infarct and border zones. Scale bar: 100μm. Histograms represent mean±SEM. A: *p<0.05 vs saline; †p<0.05 vs bFGF and MSCs groups. B: *p<0.05 vs saline; †p<0.05 vs bFGF.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4493537&req=5

Figure 4: Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) increases infarct wall thickness and reduces myocardial fibrosis. (A) Post-mortem morphometry revealed midmural scars in the left ventricular wall. Coronary venous infusion of bFGFs+MSCs increased infarct wall thickness compared to other groups. The percentage of infarct wall thickness to septal wall thickness was greatest in the bFGF+MSCs group. (B) Masson's trichrome staining showed decreased collagen content in the MSCs and bFGF+MSCs groups both in the infarct and border zones. Scale bar: 100μm. Histograms represent mean±SEM. A: *p<0.05 vs saline; †p<0.05 vs bFGF and MSCs groups. B: *p<0.05 vs saline; †p<0.05 vs bFGF.

Mentions: Gross morphologic analysis revealed midmural scars in the LV anterior and anteroseptal walls (Figure 4A). The average infarct wall thickness was increased in the bFGF+MSCs group (8.2±0.2mm) compared with saline (4.8±0.1mm), bFGF (6.2±0.2mm), and MSCs (6.6±0.1mm) groups (all p<0.05; Figure 4A). Additionally, the percentage of infarct wall to septal wall thickness was greatest in the bFGF+MSCs group (Figure 4A).


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) increases infarct wall thickness and reduces myocardial fibrosis. (A) Post-mortem morphometry revealed midmural scars in the left ventricular wall. Coronary venous infusion of bFGFs+MSCs increased infarct wall thickness compared to other groups. The percentage of infarct wall thickness to septal wall thickness was greatest in the bFGF+MSCs group. (B) Masson's trichrome staining showed decreased collagen content in the MSCs and bFGF+MSCs groups both in the infarct and border zones. Scale bar: 100μm. Histograms represent mean±SEM. A: *p<0.05 vs saline; †p<0.05 vs bFGF and MSCs groups. B: *p<0.05 vs saline; †p<0.05 vs bFGF.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493537&req=5

Figure 4: Combined administration of basic fibroblast growth factor (bFGF) and mesenchymal stem cells (MSCs) increases infarct wall thickness and reduces myocardial fibrosis. (A) Post-mortem morphometry revealed midmural scars in the left ventricular wall. Coronary venous infusion of bFGFs+MSCs increased infarct wall thickness compared to other groups. The percentage of infarct wall thickness to septal wall thickness was greatest in the bFGF+MSCs group. (B) Masson's trichrome staining showed decreased collagen content in the MSCs and bFGF+MSCs groups both in the infarct and border zones. Scale bar: 100μm. Histograms represent mean±SEM. A: *p<0.05 vs saline; †p<0.05 vs bFGF and MSCs groups. B: *p<0.05 vs saline; †p<0.05 vs bFGF.
Mentions: Gross morphologic analysis revealed midmural scars in the LV anterior and anteroseptal walls (Figure 4A). The average infarct wall thickness was increased in the bFGF+MSCs group (8.2±0.2mm) compared with saline (4.8±0.1mm), bFGF (6.2±0.2mm), and MSCs (6.6±0.1mm) groups (all p<0.05; Figure 4A). Additionally, the percentage of infarct wall to septal wall thickness was greatest in the bFGF+MSCs group (Figure 4A).

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