Intramyocardial Transplantation of Autologous Endothelial Progenitor Cells for Therapeutic Neovascularization of Myocardial Ischemia

Abstract

Background-We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia. Methods and Results-Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31ϩ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31ϩ MNCs in noncoated plates, nonadhesive cells (NA/CD31ϩ MNCs) were harvested as the endothelial progenitor cell-enriched fraction. Nonadhesive CD31Ϫ cells (NA/CD31Ϫ MNCs) were also prepared. Autologous transplantation of 10 7 NA/CD31ϩ MNCs, 10

Melhora sintomática e da capacidade de exercício após o transplante autólogo, transendocárdico, de células mononucleares da medula óssea em pacientes com cardiopatia isquêmica grave, sustentada até o sexto mês de evolução

“…Our group has carried out a study in rats showing the capacity of bone marrow cells to generate an angiogenic process, which has been demonstrated by functional and histopathologic data 55 . Similar results have been reported by other authors, such as Fuchs and Kawamoto 22,40 , who studied pigs with chronic myocardial ischemia induced by implantation of constrictors in the coronary artery, which then underwent BMMC transplantation. Before one month, the animals underwent assessment, which included histopathological analysis, and the authors reported an improvement in myocardial perfusion related to the development of new vessels.…”

“…The use of cells originating from the BM in experiments of neovascularization with the intracoronary, transendocardial, and transepicardial routes has been consistent in the international literature. In experimental models of acute and chronic myocardial ischemia 22,[33][34][35][36][37][38][39][40][41][42][43] , the implantation of bone marrow mononuclear cells (BMMC) has been able to improve myocardial contraction and perfusion 22,41,42,44,45 . Such results have been reproduced in a recent clinical phase-1 study in human beings 30,31,[46][47][48][49] , including our previous publication when the safety of that procedure was assessed 50 .…”

Endothelial progenitor cells: Implications for cardiovascular disease

“…To explain the beneficial effects on myocardial function, several theories are discussed. Neovascularization of the peri-infarct-zone through direct or paracrine means are evident (3,87). Also a reduction in ischemia and an improvement of perfusion, leading to a better regional contractility were shown (87,88).…”

Terapia celular associada à revascularização transmiocárdica laser como proposta no tratamento da angina refratária

“…The aim of this study clearly indicates the possibility of the appearance of mechanisms that can improve perfusion and, consequently, the symptomatology of this select range of patients with coronary artery disease. Although controversial, either the attempt at transdifferentiation of autologous endothelial progenitor cells, when transplanted in the ischemic myocardium for therapeutic revascularization [36], or the action of cytokines and growth factors locally applied after TMLR or associated to cells injection [37], or both, may have acted synergically, allowing the angiogenesis and subsequent functional improvement that showed the importance of the micro-environment in obtaining the desired therapeutic effect through cell therapy [38].…”