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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

Retrograde coronary venous infusion. (A) Angiogram of the left coronary artery demonstrating occlusion of the left anterior descending (LAD) coronary artery (middle) (white arrow). (B) Retrograde venography of coronary sinus. (C) A 0.014-inch exchange-length extra support guide wire was advanced to the distal portion of anterior interventricular vein (AIV). (D) Angiogram of the left coronary artery demonstrating parallel guide wire travel to the LAD (white arrowheads). (E) An over-the-wire (OTW) balloon catheter (2.5×9 mm or 2.0×9 mm) was advanced and positioned in the mid-AIV. (F) Balloon inflation and simultaneous visualization of the left coronary artery showed that balloon position was consistent with the occlusive site of the LAD (white arrow). The delivery site was within the targeted infarct zone.
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Figure 1: Retrograde coronary venous infusion. (A) Angiogram of the left coronary artery demonstrating occlusion of the left anterior descending (LAD) coronary artery (middle) (white arrow). (B) Retrograde venography of coronary sinus. (C) A 0.014-inch exchange-length extra support guide wire was advanced to the distal portion of anterior interventricular vein (AIV). (D) Angiogram of the left coronary artery demonstrating parallel guide wire travel to the LAD (white arrowheads). (E) An over-the-wire (OTW) balloon catheter (2.5×9 mm or 2.0×9 mm) was advanced and positioned in the mid-AIV. (F) Balloon inflation and simultaneous visualization of the left coronary artery showed that balloon position was consistent with the occlusive site of the LAD (white arrow). The delivery site was within the targeted infarct zone.

Mentions: Retrograde coronary venous infusion was performed as previously described 21. From LAD coronary angiography, the position of over-the-wire (OTW) balloon catheter was consistent with the occlusive site of the LAD (Figure 1). The balloon was inflated, and the selected perfusion medium was rapidly injected into the anterior interventricular vein (AIV). The balloon remained inflated for 10 minutes post injection to achieve maximum local delivery.


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)

Retrograde coronary venous infusion. (A) Angiogram of the left coronary artery demonstrating occlusion of the left anterior descending (LAD) coronary artery (middle) (white arrow). (B) Retrograde venography of coronary sinus. (C) A 0.014-inch exchange-length extra support guide wire was advanced to the distal portion of anterior interventricular vein (AIV). (D) Angiogram of the left coronary artery demonstrating parallel guide wire travel to the LAD (white arrowheads). (E) An over-the-wire (OTW) balloon catheter (2.5×9 mm or 2.0×9 mm) was advanced and positioned in the mid-AIV. (F) Balloon inflation and simultaneous visualization of the left coronary artery showed that balloon position was consistent with the occlusive site of the LAD (white arrow). The delivery site was within the targeted infarct zone.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Retrograde coronary venous infusion. (A) Angiogram of the left coronary artery demonstrating occlusion of the left anterior descending (LAD) coronary artery (middle) (white arrow). (B) Retrograde venography of coronary sinus. (C) A 0.014-inch exchange-length extra support guide wire was advanced to the distal portion of anterior interventricular vein (AIV). (D) Angiogram of the left coronary artery demonstrating parallel guide wire travel to the LAD (white arrowheads). (E) An over-the-wire (OTW) balloon catheter (2.5×9 mm or 2.0×9 mm) was advanced and positioned in the mid-AIV. (F) Balloon inflation and simultaneous visualization of the left coronary artery showed that balloon position was consistent with the occlusive site of the LAD (white arrow). The delivery site was within the targeted infarct zone.
Mentions: Retrograde coronary venous infusion was performed as previously described 21. From LAD coronary angiography, the position of over-the-wire (OTW) balloon catheter was consistent with the occlusive site of the LAD (Figure 1). The balloon was inflated, and the selected perfusion medium was rapidly injected into the anterior interventricular vein (AIV). The balloon remained inflated for 10 minutes post injection to achieve maximum local delivery.

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