Bone marrow stem cells regenerate infarcted myocardium

Abstract: Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self‐renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC‐derived myocardial regeneration resulted in improved cardiac function and survival.

[1]  Federica Limana,et al.  Mobilized bone marrow cells repair the infarcted heart, improving function and survival , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Neil D. Theise,et al.  Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell , 2001, Cell.

[3]  D. Bodine,et al.  Transplanted Adult Bone Marrow Cells Repair Myocardial Infarcts in Mice , 2001, Annals of the New York Academy of Sciences.

[4]  D. Durocher,et al.  The cardiac transcription factors Nkx2‐5 and GATA‐4 are mutual cofactors , 1997, The EMBO journal.

[5]  Xin Wang,et al.  Purified hematopoietic stem cells can differentiate into hepatocytes in vivo , 2000, Nature Medicine.

[6]  S. Mckercher,et al.  Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. , 2000, Science.

[7]  H. Blau,et al.  From marrow to brain: expression of neuronal phenotypes in adult mice. , 2000, Science.

[8]  David M. Bodine,et al.  Bone marrow cells regenerate infarcted myocardium , 2001, Nature.

[9]  R. Mulligan,et al.  Dystrophin expression in the mdx mouse restored by stem cell transplantation , 1999, Nature.

[10]  M. Robert-Guroff IgG surfaces as an important component in mucosal protection , 2000, Nature Medicine.

[11]  A. Nienhuis,et al.  Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor. , 1994, Blood.

[12]  S. Homma,et al.  Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function , 2001, Nature Medicine.

[13]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[14]  J. Saffitz,et al.  Rapid turnover of connexin43 in the adult rat heart. , 1998, Circulation research.

[15]  A. Katz,et al.  Evidence that human cardiac myocytes divide after myocardial infarction. , 2001, The New England journal of medicine.