Scaffold-Based Transplantation of Vascular Endothelial Growth Factor—Overexpressing Stem Cells Leads to Neovascularization in Ischemic Myocardium but Did Not Show a Functional Regenerative Effect

Abstract

The transplantation of skeletal myoblasts (SkM) might improve cardiac function after myocardial infarction via paracrine action. We used scaffold-based cell transfer by using vascular endothelial growth factor (VEGF)-overexpressing myoblasts. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were transfected with pCINeo-VEGF(121) and seeded on polyurethane (PU) scaffolds. The seeded scaffolds were epicardially implanted in rats 2 weeks after myocardial infarction (group: PU-VEGF-SkM). Before this intervention and 6 weeks later, pressure/volume loops were analyzed followed by histology. Additional study groups (n = 10 per group) were injected with VEGF-overexpressing myoblasts (Inj-VEGF-SkM) or unmodified myoblasts (Inj-SkM) or underwent a sham operation. Overexpression of VEGF was verified in vitro. The transplantation of growth factor producing myoblast-seeded scaffolds resulted in enhanced angiogenesis of ischemically damaged myocardium in vivo. However, the infarction size was not reduced. In group Inj-SkM, hemodynamics remained unchanged. Systolic function as measured by dP/dt(max) was not significantly altered in PU-VEGF-SkM (preinterventionally 2,156 ± 1,222 mmHg vs. postinterventionally 2,134 ± 850 mmHg). Other systolic function and diastolic function parameters as measured by dP/dt(min), tau, and pressure half-time were not restored in groups PU-VEGF-SkM and Inj-VEGF-SkM either. Transplantation of VEGF-overexpressing skeletal myoblasts leads to neovascularization in infarcted hearts. No functional myocardial recovery was observed. Scaffold-based transfer of genetically-modified cells remains a useful tool to study paracrine stem cell action.

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Nevertheless, statistical analysis showed no significant changes in infarct size between groups. Regarding cardiac function, only the HGF overexpressing SM-NFs treated group showed a significant improvement from baseline at the end of the study [94,95]. These results are in correlation with the study of Giraud M.N.…”

“…Two years later, in 2012, a couple of interesting studies were performed in the same direction. On one hand, von Wattenwyl R. et al used VEGF-overexpressing myoblasts (5x10 6 ) seeded on PU-NFs [94]. On the other hand, Poppe A. et al transfected SM (5x10 6 ) with HGF and then seeded them on the same DDS [95].…”

Gelatin-chondroitin-6-sulfate-hyaluronic acid scaffold seeded with vascular endothelial growth factor 165 modified hair follicle stem cells as a three-dimensional skin substitute

“…Facilitation of the process of vascularization is thus an unmet clinical need in the field of skin tissue engineering [ 4 – 6 ]. Composite delivery system construction [ 7 , 8 ], screening of cell-seed types [ 9 – 12 ], incorporation of effective active factors [ 13 , 14 ] and applying genetically-modified cells [ 10 – 12 ] can promote early vascularization of tissue-engineered skin. Gelatin–chondroitin-6-sulfate–hyaluronic acid (Gel-C6S-HA) scaffolds are known to be hydrophilic with good tissue compatibility and biodegradability [ 15 , 16 ].…”

Cutting-Edge Regenerative Medicine Technologies for the Treatment of Heart Valve Calcification

“…On one hand, it would be possible to introduce genome modifications in cells already applied in TEHVs to induce paracrine mechanisms able to foster cell differentiation. On this basis, VEGF-overexpressing stem cells transplanted in the ischemic myocardium induced an improvement in vascularization [142]. Indeed, MSCs engineered to express Akt did not only participate to the repair of the infarcted heart, but also improved cardiac function [143].…”