Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.
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.


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 7x10(5) 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.
Yoon
Young-Sup
YS
Division of Cardiovascular Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge St, Boston, Mass 02135, USA. young.yoon@tufts.edu
Park
Jong-Seon
JS
Tkebuchava
Tengiz
T
Luedeman
Corinne
C
Losordo
Douglas W
DW
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000637:transplantation; D002999:Clone Cells / Q000637:transplantation; D005260:Female; D008297:Male; D039902:Multipotent Stem Cells / Q000473:pathology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D011183:Postoperative Complications / Q000209:etiology* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D014463:Ultrasonography