Cardiac repair and regeneration: the Rubik’s cube of cell therapy for heart disease

Abstract

Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.

Isolation, Characterization and Differentiation Potential of Cardiac Progenitor Cells in Adult Pigs

“…However, the ability of MSCs to transdifferentiate into cardiomyocytes is highly controversial (Rose et al 2008) and their beneficial effect is thought to derive mainly from their influence on neovascularization of the ischemic tissue and their protection of resident cells (Gnecchi et al 2008). This property, together with their low immunogenicity (Aggarwal et al 2005), make MSCs an efficient cellular vehicle for delivering therapeutic substances to the myocardial lesion (Boudoulas et al 2009), promoting their use in allogeneic recipients as well.…”

Meeting the Need for Regenerative Therapies: Translation-Focused Analysis of U.S. Regenerative Medicine Opportunities in Cardiovascular and Peripheral Vascular Medicine Using Detailed Incidence Data

“…Several biological processes, such as inflammation, vascularization, and regenerative signaling, intersect [24][25][26][27] among these disease contexts. For this reason, we analyzed the therapeutic opportunities in cardiac and peripheral vascular medicine as a combined group referred to as ''cardio/vascular.''…”

“…To date, the absence of scientific data on mechanism(s) of action is still a significant gap standing in the way of a regenerative therapy to halt progression to heart failure. 49,58 Cells from different source may not be equally effective at all stages, 25 the same will be true for regenerative factors. Although these therapies remain in their infancy, the market size and medical need justify the continued effort and investment.…”

Dynamic Relationships of Collagen Extracellular Matrices on Cardiac Differentiation of Human Mesenchymal Stem Cells

“…Such pathological insults place increasing mechanical demands on surviving cardiomyocytes (Boudoulas & Hatzopoulos, 2009). As cardiomyocytes have limited regenerative potential, loss of functional healthy tissue and subsequent left ventricular (LV) remodelling, eventually leads to pathological hypertrophic cardiomyopathy.…”