PMID- 15754420 OWN - NLM STAT- MEDLINE DCOM- 20050722 LR - 20181113 IS - 1673-1581 (Print) IS - 1673-1581 (Linking) VI - 6 IP - 4 DP - 2005 Apr TI - Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. PG - 242-8 AB - 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. CONCLUSION: Transplantation of hMSCs could transdifferentiate into cardiomyocytes and regenerate vascular structures, contributing to functional improvement. FAU - Wang, Jian-an AU - Wang JA AD - Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China. FAU - Fan, You-qi AU - Fan YQ FAU - Li, Chang-ling AU - Li CL FAU - He, Hong AU - He H FAU - Sun, Yong AU - Sun Y FAU - Lv, Bin-jian AU - Lv BJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - J Zhejiang Univ Sci B JT - Journal of Zhejiang University. Science. B JID - 101236535 RN - 0 (Biomarkers) SB - IM MH - Animals MH - Biomarkers/analysis MH - Bone Marrow Cells/*cytology MH - Bone Marrow Transplantation MH - Cells, Cultured MH - Humans MH - Immunohistochemistry MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Myocardial Infarction/*physiopathology/*surgery MH - Rabbits MH - Survival Rate MH - Time Factors PMC - PMC1389731 EDAT- 2005/03/09 09:00 MHDA- 2005/07/23 09:00 PMCR- 2005/04/01 CRDT- 2005/03/09 09:00 PHST- 2005/03/09 09:00 [pubmed] PHST- 2005/07/23 09:00 [medline] PHST- 2005/03/09 09:00 [entrez] PHST- 2005/04/01 00:00 [pmc-release] AID - 10.1631/jzus.2005.B0242 [doi] PST - ppublish SO - J Zhejiang Univ Sci B. 2005 Apr;6(4):242-8. doi: 10.1631/jzus.2005.B0242.