Stem Cell Research

Abstract

Cardiovascular Disease and Adult Healing Cells: From Bench Top to Bedside

Henry E. Young, Ioannis J. Limnios, Frank Lochner, George McCommon, Gypsy F. Black, Julie A. Coleman, Kristina C. Hawkins, Shanna Williams and Asa C. Black, Jr.

Cardiovascular disease, especially ischemic heart disease resulting from coronary artery disease (CAD), is one of the major causes of death and disability in the United States. Even though the dead myocardial cells can be replaced by scar tissue in the healing process, the resulting myocardium cannot function as well as the preinfarcted myocardium, because scar tissues cannot contract. This “normal” healing process results in decreased cardiac output, which can lead to heart failure. Moreover, the scar tissue has abnormal electrical properties, which can lead to sometimes fatal arrhythmias. Previous studies demonstrated that when Lac-Z-labeled healing cells were infused into two animal models of myocardial infarction, that these cells were found to be located within the myocardium, the cardiac skeleton, and the vasculature undergoing repair. These results suggested that healing cells have the potential to repair damaged hearts. The current series of studies were undertaken to determine whether healing cells customarily reside in normal non-injured hearts of small and large animals, and whether autologous healing cells could be infused safely into a post-myocardial infarction patient. Adult rats were euthanized following the guidelines of Mercer University’s IACUC. Adult pigs were euthanized following the guidelines of Fort Valley State University’s IACUC. The human study was performed under the guidance of the Medical Center of Central Georgia’s IRB. Animal hearts were harvested, fixed, cryosectioned, and stained with three antibodies: carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) for totipotent stem cells, stage-specific embryonic antigen-4 (SSEA-4) for pluripotent stem cells, and smooth muscle alpha-actin (IA4) for smooth muscle in the wall of the accompanying vasculature, thus serving as the positive procedural control. Cells positive for both CEA-CAM-1 and SSEA-4 were found to be located in adult rat and porcine hearts. Infusion of autologous healing cells into a post-myocardial infarcted patient resulted in an increase in their cardiac output after two successive healing cell infusions. Current IRB-approved studies are underway to assess the safety and efficacy of infused healing cells into individuals with cardiovascular disease.