Mesenchymal Stem Cell Therapy for Treatment of Cardiovascular Disease: Helping People Sooner or Later

Abstract

Despite advances in clinical management, cardiovascular disease remains the leading cause of death in America. While cardiomyocytes retain limited plasticity following maturation, the heart is grossly unable to recover from structural damage. Mesenchymal stem cell (MSC) therapy, through its promise of repair and regeneration of cardiac tissue, represents an exciting avenue of treatment for a range of cardiovascular diseases. MSCs are relatively immunoprivileged, lacking both major histocompatibility II and T-cell co-stimulatory signal expression, and possess the unique ability to home into sites of myocardial damage when delivered systemically. Additionally, they have been shown to provide therapeutic benefit via several distinct mechanisms, the most important of which appears to be the abundant secretion of paracrine factors that promote local regeneration. In light of this, several groups have sought to precondition MSCs, using various molecular and genetic means, in order to enhance viability and growth factor secretion in the heart, following transplantation. Here, we analyze and integrate information from recent MSC studies, focusing on underlying mechanisms of MSC-associated repair in animal models of cardiac disease. Additionally, MSC pretreatment studies are organized here to examine their relative effectiveness and potential for clinical use. Data emerging from ongoing human clinical trials are also evaluated for consistency with animal studies and their therapeutic promise. Finally, we attempt to answer whether cumulative evidence from animal and human studies is suggestive of significant, clinically viable cardiac repair in acute and chronic conditions and explore ways in which future studies can enhance effectiveness of cell-based therapy.

Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage

“…Although MSCs have been considered to be hypoimmunogenic or immunoprivileged and can escape from host immune surveillance [38], we [14] and others [15,16] have reported that MSCs activate complement in the blood, leading to cell damage and impairment of function. In our previous study [14], we focused on the direct effect of complement activation on MSC viability and function, i.e., direct MAC-mediated MSC injury, using serum as the source of complement in the absence of blood cells.…”

Bone Marrow Mesenchymal Stem Cells: Biological Properties and Their Role in Hematopoiesis and Hematopoietic Stem Cell Transplantation

“…While a rapidly growing number of published reports over the last years has corroborated MSCs' potential to contribute to cell-based therapies, not only in the context of GVHD and HSCT, but also for bone and cartilage repair [184,185], cardiovascular diseases [186,187] and central nervous system disorders [188,189], the potential hazards from their use have only recently drawn scientists' attention.…”

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

“…MSCs are considered as a cellular substrate for the cardiac repair because of their presumptive plasticity, genetic stability, and immune tolerance (Trivedi et al, 2010). Furthermore, the accessibility, ease of handling, and enormous expansion potential of MSCs, together with their capacity for self-renewal and amenability to allogenic transplantation (Amado et al, 2005;Dai et al, 2005), provide a nearly unlimited supply of cells for therapeutic applications.…”