Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function.
OBJECTIVE
The present study was designed to test whether transplantation of human bone marrow-derived mesenchymal stem cells (hMSCs) in New Zealand rabbits with myocardial infarction can improve heart function; and whether engrafted donor cells can survive and transdifferentiated into cardiomyocytes.


METHODS
Twenty milliliters bone marrow was obtained from healthy men by bone biopsy. A gradient centrifugation method was used to separate bone marrow cells (BMCs) and red blood cells. BMCs were incubated for 48 h and then washed with phosphate-buffered saline (PBS). The culture medium was changed twice a week for 28 d. Finally, hematopoietic cells were washed away to leave only MSCs. Human MSCs (hMSCs) were premarked by BrdU 72 h before the transplantation. Thirty-four New Zealand rabbits were randomly divided into myocardial infarction (MI) control group and cell treated group, which received hMSCs (MI+MSCs) through intramyocardial injection, while the control group received the same volume of PBS. Myocardial infarction was induced by ligation of the left coronary artery. Cell treated rabbits were treated with 5 x 10(6) MSCs transplanted into the infarcted region after ligation of the coronary artery for 1 h, and the control group received the same volume of PBS. Cyclosporin A (oral solution; 10 mg/kg) was provided alone, 24 h before surgery and once a day after MI for 4 weeks. Echocardiography was measured in each group before the surgery and 4 weeks after the surgery to test heart function change. The hearts were harvested for HE staining and immunohistochemical studies after MI and cell transplantation for 4 weeks.


RESULTS
Our data showed that cardiac function was significantly improved by hMSC transplantation in rabbit infarcted hearts 4 weeks after MI (ejection fraction: 0.695+/-0.038 in the cell treated group (n=12) versus 0.554+/-0.065 in the control group (n=13) (P<0.05). Surviving hMSCs were identified by BrdU positive spots in infarcted region and transdifferentiated into cardiomyocytes characterized with a positive cardiac phenotype: troponin I.


CONCLUSIONS
Transplantation of hMSCs could transdifferentiate into cardiomyocytes and regenerate vascular structures, contributing to functional improvement.
Wang
Jian-an
JA
Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Fan
You-qi
YQ
Li
Chang-ling
CL
He
Hong
H
Sun
Yong
Y
Lv
Bin-jian
BJ
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000601:surgery*; D011817:Rabbits; D015996:Survival Rate; D013997:Time Factors
D015415:Biomarkers