Purified human bone marrow multipotent mesenchymal stem cells regenerate infarcted myocardium in experimental rats.
Recent findings suggest the feasibility of cardiac repair by transplantation of bone marrow mesenchymal stem cell (MSCs). However, it remains controversial regarding which cell type is the best source for transplanting into the ischemic heart because of lack of well-defined cell markers. In this study, we investigated the in vitro and in vivo effects of the novel multipotent marrow mesenchymal stem cells (MMSCs) from human bone marrow. Pluripotent markers (Oct4, Bmi1, and Abcg2) and vascular endothelial growth factor (VEGF) were detected by RT-PCR and immunofluorescence in MMSCs. Myocardial differentiation was induced in the expanded MMSC cultures by treatment with 5-azacyline. Expressions of VEGF in the animals transplanted with MMSCs were markedly increased in comparison with the animals injected with fibroblasts or saline at both mRNA and protein levels. VEGF expression was observed in both transplanted MMSCs and recipient cardiomyocytes by immunofluorescence. Confocal immunofluorescence microscopy revealed the specific markers for cardiomyocytes and endothelial cells in transplanted MMSCs 14 days after transplantation. Vessel count was increased and left ventricular function improved post-MMSC transplantation. These results indicate that transplantation of purified MMSCs from human bone marrow upregulated VEGF expression, enhanced angiogenesis, and improved the functional recovery following myocardial infarction in rats.
Zhang
Shaoheng
S
Stem Cell Research Center, Peking University, Hai Dian District, Beijing, China.
Jia
Zhuqing
Z
Ge
Junbo
J
Gong
Lizhong
L
Ma
Yanling
Y
Li
Tao
T
Guo
Jingxuan
J
Chen
Ping
P
Hu
Qikuan
Q
Zhang
Ping
P
Liu
Yonggang
Y
Li
Zhaoping
Z
Ma
Kangtao
K
Li
Linsong
L
Zhou
Chunyan
C
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000379:methods; D002454:Cell Differentiation; D002469:Cell Separation / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D039902:Multipotent Stem Cells / Q000737:chemistry / Q000502:physiology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics; D016277:Ventricular Function, Left
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C069077:BMI1 protein, human; D015415:Biomarkers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D042461:Vascular Endothelial Growth Factor A; D063150:Polycomb Repressive Complex 1