Increased Potency of Cardiac Stem Cells Compared with Bone Marrow Mesenchymal Stem Cells in Cardiac Repair

Abstract

Whereas cardiac-derived c-kit؉ stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (MSCs) are undergoing clinical trials testing safety and efficacy as a cell-based therapy, the relative therapeutic and biologic efficacy of these two cell types is unknown. We hypothesized that human CSCs have greater ability than MSCs to engraft, differentiate, and improve cardiac function. We compared intramyocardial injection of human fetal CSCs (36,000) with two doses of adult MSCs (36,000 and 1,000,000) or control (phosphate buffered saline) in nonobese diabetic/severe combined immune deficiency mice after coronary artery ligation. The myocardial infarction-induced enlargement in left ventricular chamber dimensions was ameliorated by CSCs (p < .05 for diastolic and systolic volumes), as was the decline in ejection fraction (EF; p < .05). Whereas 1 ؋ 10 6 MSCs partially ameliorated ventricular remodeling and improved EF to a similar degree as CSCs, 36,000 MSCs did not influence chamber architecture or function. All cell therapies improved myocardial contractility, but CSCs preferentially reduced scar size and reduced vascular afterload. Engraftment and trilineage differentiation was substantially greater with CSCs than with MSCs. Adult-cultured c-kit ؉ CSCs were less effective than fetal, but were still more potent than high-dose MSCs. These data demonstrate enhanced CSC engraftment, differentiation, and improved cardiac remodeling and function in ischemic heart failure. MSCs required a 30-fold greater dose than CSCs to improve cardiac function and anatomy. Together, these findings demonstrate a greater potency of CSCs than bone marrow MSCs in cardiac repair. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:116 -124

Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart

“…Research from several laboratories, including ours, suggests that stem cells hold immense potential for cardiac repair and regeneration. [1][2][3][4] Clinical use of adult stem cells is a reality today and many stem cell types, including bone marrow-derived mesenchymal stem cells (MSCs), 5 bone marrow cells, 7,8 cardiac-derived cardiac progenitor, 6 and cardio-sphere derived cells 9 have been tested. The beneficial effects of tested cell therapies on cardiac structure and function have been modest and most studies to date have not been adequately powered to document efficacy.…”

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

“…Animal studies have demonstrated that transplantation of cardiac resident stem cells (CRSCs) exerts cardioprotection through release of paracrine factors and, to a lesser extent, trans-differentiation into cardiomyocytes, endothelial, and vascular smooth muscle cells [3,4,[7][8][9]. Moreover, CRSCs have been shown to engraft better in infarcted mouse myocardium and are more effective than bone marrowderived mesenchymal stem cells (BMSCs) in cardiac repair [8]. These preclinical and clinical findings have reinforced the approach of using cardiac-specific stem cells to treat cardiac disease for the highest probability of therapeutic success.…”

Stem cells for the treatment of heart failure

“…of cells committed towards a cardiac lineage [5]. This superiority remains present even if the paracrine hypothesis is prevailing, as shown by the finding that the production of potentially cardio-protective growth factors is higher with cells derived from the right ventricle (cardiospheres) than with extracardiac cells derived from bone marrow or adipose tissue [6].…”