Cardiovascular disease (CVD), principally heart disease and stroke, is the leading cause of death for both men and women, among all racial and ethnic groups in developed countries. It is also an increasing problem for developing countries. Almost 1 million Americans die of CVD each year, which is approximately 42% of all deaths. Complications of CVD often results in a long?term, severe reduction in quality of life. The limited ability of the damaged heart to heal, and of new blood vessels to grow after myocardial infarction are the main reasons for these long term complications, specifically of heart failure. Our laboratory focuses on the role of stem cells in cardiovascular regeneration. We are isolating rare stem cell populations from the bone marrow of adults. These cells called Multipotent Adult Progenitor Cells (MAPCs) represent a subpopulation of Mesenchymal Stromal Cells (MSC) but have the unique properties of being able to differentiate into almost all tissues of the body. When these MAPCs are injected into a developing mouse embryo, they contribute to all organ structures (except the germ line) properties that make them similar to embryonic stem cells except that they are derived from adults, not embryos. We are investigating the molecular mechanisms that enable MAPCs to differentiate into endothelial and smooth muscle cells, the major cell populations found in normal blood vessel, as well as cardiomyocytes. At present we are testing characterized MAPCs in rat and mouse injury models. We have developed a hind limb ischemia model in rats and are testing and comparing different stem cell types (MAPC, MSC and ES-cell) in their ability to improve not only the perfusion but also the function of ischemic hind limbs. Understanding the function including the molecular and cellular pathways of stem cells is critical to the design and development of new therapies for cardiovascular diseases. We anticipate that by better understanding the biology of these adult stem cells and their role in cardiac regeneration, new therapeutic interventions may be developed to improve the outcome of the many patients that suffer from chronic cardiac diseases.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
U.S. National Heart Lung and Blood Inst
United States
Zip Code
True, Andrea L; Olive, Michelle; Boehm, Manfred et al. (2007) Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide. Circ Res 101:893-901
Ganesh, Lakshmanan; Yoshimoto, Takanobu; Moorthy, Narayani C et al. (2006) Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis. Mol Cell Biol 26:3864-74
Yoshimoto, Takanobu; Boehm, Manfred; Olive, Michelle et al. (2006) The arginine methyltransferase PRMT2 binds RB and regulates E2F function. Exp Cell Res 312:2040-53
Matoba, Satoaki; Kang, Ju-Gyeong; Patino, Willmar D et al. (2006) p53 regulates mitochondrial respiration. Science 312:1650-3
Quasnichka, Helen; Slater, Sadie C; Beeching, Cressida A et al. (2006) Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression. Circ Res 99:1329-37
Nallamshetty, Shriram; Crook, Martin; Boehm, Manfred et al. (2005) The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication. FEBS Lett 579:6529-36
Li, Rong; Faria, Teresa N; Boehm, Manfred et al. (2004) Retinoic acid causes cell growth arrest and an increase in p27 in F9 wild type but not in F9 retinoic acid receptor beta2 knockout cells. Exp Cell Res 294:290-300
Boehm, Manfred; Olive, Michelle; True, Andrea L et al. (2004) Bone marrow-derived immune cells regulate vascular disease through a p27(Kip1)-dependent mechanism. J Clin Invest 114:419-26