Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats.
BACKGROUND
Bone marrow-derived mesenchymal stem cells (MSCs) are of great therapeutic potential after myocardial ischemic injury. However, little is known about the biological characteristics of MSCs in patients with coronary artery disease and their effects on infracted myocardium. The present study evaluated the biological characteristics of MSCs from patients with coronary artery disease and their effects after being transplanted into infarcted myocardium using a rat model.


METHODS
Sternal bone marrow aspirates were taken at the time of coronary artery bypass graft surgery. Mononuclear cells isolated from bone marrow were cultured based on plastic adherence. The morphology and growth characteristics of MSCs were observed in primary and successive passages. A myocardial infarction model was created in 27 adult rats. Two weeks later, animals were randomized into two groups: culture medium (group I, n=13) or MSCs (2x10(6)) from early passages labeled with BrdU (group II, n=14) were injected into the infarcted myocardium. Echocardiography, histological examination, and reverse transcription-polymerase chain reaction (RT-PCR) were performed four weeks after cell transplantation.


RESULTS
Flow cytometry analyses demonstrated that adherent spindle cells from bone marrow are mesenchymal stem cells (positive for CD29 and CD44, but negative for CD34 and CD45). Growth curves showed that MSCs have great proliferative capability especially at early passages. MSCs implantation in the infarcted border zone improved left ventricular function significantly in group II compared with group I. However, despite improved left ventricular function, we did not observe significant regeneration of cardiac myocytes. Immunohistochemistry revealed only the expression of desmin in the engrafted MSCs, a marker of premature myocyte. Moreover, the improved left ventricular function in this study seemed to be secondary to the beneficial reverse remodeling induced by the increase of collagen in infarcted zone, the decrease in the adjacent myocardium, and the increase of neovascularization (capillary density: 192+/-7.8/mm2 in group II vs. 165+/-5.9/mm2 in group I, P<0.05). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the expression levels of collagen I, collagen III, SDF-1 (stromal cell-derived factor-1), and VEGF (vascular endothelia growth factor) in the infarcted border zone were significantly higher in the MSCs treated group.


CONCLUSIONS
The MSCs from patients with coronary artery disease have a typical phenotype with highly proliferative potential and the engrafted MSCs may regulate extracellular collagens and cytokines to prevent the ventricular scar from pathologic thinning and attenuate the contractile dysfunction of the infarcted heart.
Hou
Mai
M
Research Center for Cardiovascular Regeneration Medicine in Fu-Wai Hospital, the Ministry of Health, Department of Cardiovascular Surgery, Cardiovascular Institute and Fuwai Heart Hospital, CAMS, PUMC, Beijing 100037, PR China.
Yang
Ke-ming
KM
Zhang
Hao
H
Zhu
Wei-Quan
WQ
Duan
Fu-jian
FJ
Wang
Hao
H
Song
Yun-hu
YH
Wei
Ying-jie
YJ
Hu
Sheng-shou
SS
D000818:Animals; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous