Published online before print June 14, 2004, doi: 10.1161/01.CIR.0000134696.08436.65
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(Circulation. 2004;109:3154-3157.)
© 2004 American Heart Association, Inc.
Brief Rapid Communications |
Unexpected Severe Calcification After Transplantation of Bone Marrow Cells in Acute Myocardial Infarction
From the Divisions of Cardiovascular Medicine and Research, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass.
Correspondence to Dr Douglas W. Losordo or Dr Young-sup Yoon, Cardiovascular Research, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail douglas.losordo{at}tufts.edu or young.yoon@tufts.edu
Received February 17, 2004; de novo received April 18, 2004; revision received May 17, 2004; accepted May 19, 2004.
Background— There has been a rapid increase in the number of clinical trials using unselected bone marrow (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 studies using BM-derived cells for treatment of various cardiac diseases.
Methods and Results— 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 7x105 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.
Conclusions— These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.
Key Words: myocardial infarction • calcium • cells • transplantation
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