What's New in Cardiac Cell Therapy? Allogeneic Bone Marrow Stromal Cells as “Universal Donor Cells”

Abstract

Cardiac cell therapies offer distinct and exciting advantages over current treatments to prevent postinfarction heart failure because they can reverse ventricular remodeling and improve function, but only if the implanted stem cells contribute biological functions and achieve prolonged engraftment within the hostile environment of the damaged heart. Unfortunately, function is diminished in autologous stem cells isolated from older patients and those with comorbidities, and so clinical trials testing the implantation of healthy, allogeneic bone marrow-derived stromal cells (MSCs) isolated from young donors are currently underway. MSCs are unique because, in addition to exerting paracrine effects that restore blood flow and recruit endogenous stem cells to the infarct, they exhibit immune-modulating properties in culture that-if retained after allogeneic implantation-imply the cells may escape immune recognition within the heart. At present, the scope of MSC immune modulation after implantation is unclear.

Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy

“…Together, our findings strongly support the ongoing development of allogeneic MSC therapy in patients with a variety of chronic conditions. 8,15,29,30,34 …”

Effect of Aging on Human Mesenchymal Stem Cell Therapy in Ischemic Cardiomyopathy Patients

“…While some proponents believe advanced stem cell donor age results in diminished function (17-21), other studies raise a clinically relevant issue as to whether recipient age is a crucial factor limiting response to cell therapy (22-24). This has led to the notion that MSC therapy outcome depends not only on stem cell age, and thus function, but also recipient age and comorbidities (9,22).…”

“…This has led to the notion that MSC therapy outcome depends not only on stem cell age, and thus function, but also recipient age and comorbidities (9,22). Indeed, reduced responsiveness as a function of donor age would be a major limitation to the emerging development of cell therapy for heart disease, given the increasing incidence and morbidity of heart disease with age (25).…”

Concise Review: Immunomodulatory Properties of Mesenchymal Stem Cells in Cellular Transplantation: Update, Controversies, and Unknowns

“…Similarly, the Revascor trial is another randomized, placebo‐controlled multicenter trial that assesses the safety and feasibility of three different doses of allogeneic MSCs delivered into the myocardium of patients with chronic heart failure. After 3 months, their preliminary results were also reported online (http://www.angioblast.com) and described a significant improvement in the overall ventricular function [50]. More importantly, promising results of the phase II trial were recently reported at the 2011 meeting of the American Heart Association (held in Orlando, FL).…”