Progress and prospects: Cell based regenerative therapy for cardiovascular disease

Abstract

Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials. Gene Therapy (2006) 13, 659-671.

Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells

“…Such an increase in the arterial supply is critical to treatment of ischemic vascular diseases. This finding was unexpected because it is not observed in microvessels induced by overexpression of growth factors such as VEGF-165 (5). Further studies will be needed to elucidate the mechanism responsible for this effect that may result from flow-induced changes or factors produced by the implanted Bcl-2-HUVECs.…”

“…Although attempts to induce angiogenesis with cytokines such as VEGF have shown benefit in some animal models (3), the resulting neovessels remain disorganized and immature (4). In controlled clinical trials, VEGF monotherapy fails to increase perfusion because it does not enlarge arterioles feeding the site, a process referred to as arteriogenesis (5). Infusion of stem cells to initiate vasculogenesis has been attempted experimentally, but little is yet known about how to effectively use this approach (6).…”

Antioxidant Gene Therapy for Cardiovascular Disease

“…Several clinical trials addressing the safety, feasibility, and efficacy of fractioned or nonfractioned bone marrow cells delivered via either the intracoronary or transendocardial route in the treatment of acute myocardial infarction or chronic ischemic heart failure have been performed, with many showing an improvement in myocardial function. 87 Despite these encouraging results, the mechanisms by which transplanted cells exert their effects are still under debate. Experimental results regarding the capability of bone marrow hematopoietic stem cells to differentiate into cardiomyocytes and regenerate infarcted myocardium in a mouse model are controversial.…”

Gene and Cell Therapy for Heart Failure

“…Little evidence exists that skeletal myoblasts undergo transdifferentiation, and it has been postulated that the mechanical effects of cell transfer in terms of modification of the scar by a new inert tissue mass may in itself favorably alter ventricular geometry and cardiac output (27). Another plausible mechanism of benefit from cell transfer, which has been suggested primarily for skeletal myoblasts, is cell integration or electromechanical coupling (44).…”