Innovita Research Foundation

I.R.F. / Aging news / General / 07082701

Cardiac Repair with Bone Marrow Cells. Experimental Survey.
Posted on: August 27, 2007

Heart failure associated with ischemic heart disease is a growing, worldwide epidemic. Traditionally, the myocardium has been considered to have a very limited capacity for self-regeneration. Therefore, the loss of vasculature and cardiac muscle cells that occurs during myocardial infarction leads to progressive heart failure in up to 50% of survivors. Because no currently available therapy is directly targeted toward replacement of lost cardiac tissue, the recent identification of adult stem cells has ignited significant interest in the possibility of using these cells for cardiovascular regeneration.

A growing body of evidence suggests that the adult bone marrow (BM) contains stem and/or progenitor cells, which can give rise to endothelial cells. With the recent demonstration that administration of whole or selected BM cells or selected BM-derived circulating cells such as endothelial progenitor cells or hematopoietic stem cells could induce neovascularization and restore cardiac function after myocardial infarction in animal models, the use of BM cells has been suggested as a possible clinical strategy for the treatment of ischemic heart diseases and heart failure. Largely because of the ease of harvest and apparent lack of requirement for ex vivo manipulation, there has been a rapid increase in the number of clinical trials using unselected BM cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any preclinical or clinical trials using BM-derived cells for treatment of various cardiac diseases. In scientific research seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7·105 DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification.

These results demonstrate that direct transplantation of unselected BM cells into the acutely infracted myocardium may induce significant intramyocardial calcification.

Source: Young-Sup Yoon, MD, PhD; Jong-Seon Park, MD, PhD; Tengiz Tkebuchava, MD, PhD; Corinne Luedeman, BS; Douglas W. Losordo, MD; Unexpected Severe Calcification After Transplantation of Bone Marrow Cells in Acute Myocardial Infarction Circulation. 2004;109:3154-3157.
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