Transplantation of Autologous Endothelial Cells Induces Angiogenesis

Abstract

This study examined the feasibility and efficacy of autologous endothelial cell (EC) transplantation using a fibrin matrix in the ischemic myocardium of sheep. Four weeks after placing an ameroid constrictor in the circumflex artery of 12 adult sheep, four animals (EC group) were subjected to EC transplantation. In four others (saline [SAL] group) saline with added inactivated cells was injected and four animals served as controls. Eight weeks after treatment the animals were sacrificed to assess histology and ultrastructure. Eight weeks after injection, ventricular function was markedly improved in the EC transplant group, but had deteriorated in the SAL and control groups. Myocardial blood flow was also increased in the EC group. Histology and electron microscopy revealed extensive neovascularization after EC transplantation and improved myocardial appearance. Heterotopic transplantation of EC within a fibrin matrix enhances neovascularization, increases myocardial blood flow, and improves left ventricular function.

Prevascularized Microtemplated Fibrin Scaffolds for Cardiac Tissue Engineering Applications

“…13 Additionally, fibrin induces neovascularization within ischemic myocardium and reduces infarct expansion, with enhanced neovascularization in ischemic myocardium observed following injection of fibrin gels alone or in conjunction with cells. [12][13][14][15] The observed neovascularization effects of fibrin fit with the well-established role of fibrin degradation products in the induction of angiogenesis, 16 and further demonstrate the suitability of fibrin as a scaffold biomaterial.…”

Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis

“…Transplanted ECs were incorporated into the new vessels and increased regional perfusion in myocardial scar tissue but failed to improve global function. Chekanov and colleagues 38 administered autologous ECs into the ischemic myocardium of sheep using a fibrin matrix and demonstrated enhancement of neovascularization with improved left ventricular function. In tumor angiogenesis models, 39,40 implanted mature ECs similarly contributed to host neovascularization and tumor growth; furthermore, genetic modification of the ECs with the antiapoptotic gene Bcl-2 enhanced the effects of cell implantation.…”

The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell Homing for Treatment of Vascular Disease

“…10 Furthermore, fibrin augments angiogenesis both in vitro and in vivo, 28,75 wherein transplantation of endogenous endothelial cells within fibrin hydrogels promotes capillary formation in ischemic myocardium in sheep. 14 Alginate, a naturally occurring anionic polymer typically obtained from brown seaweed, is another hydrogel-forming biomaterial that has been extensively studied for many biomedical applications. 39 Benefits to using alginate include its high biocompatibility, structural similarities to ECMs, low toxicity, relatively low cost, and mild gelation by addition of divalent cations.…”