Effects of mesenchymal stem cell transplantation on extracellular matrix after myocardial infarction in rats.
OBJECTIVE
The present study was to determine the effects of mesenchymal stem cell (MSC) transplantation into ischemic myocardium on left ventricular (LV) function and remodeling, especially the changes in extracellular matrix (ECM) and in transforming growth factor (TGF)-beta1 after myocardial infarction (MI).


METHODS
In this study, we investigated the changes in ECM involving collagen type I, collagen type III, matrix metalloproteinase (MMP)-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and in TGF-beta1 mRNA expressions by using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization after MSC transplantation into infarcted myocardium in rats. Protein expressions were detected by immunohistochemistry and western blot. Seven and 28 days after coronary artery ligation, hemodynamic evaluations were performed.


RESULTS
Heart : body weight ratio in the MI+MSC group decreased after MSC transplantation into infarcted myocardium compared with the MI group. However, LV systolic pressure (LVSP) and LV peak velocities of contraction and relaxation (+dP/dtmax and -dP/dtmax) significantly increased compared with the MI group (P<0.01). There was marked up-regulation of mRNA transcription for ECM and TGF-beta1 proteins in MI rats. Immunohistochemical and western blot studies confirmed that the expressions of these ECM and TGF-beta1 proteins were significantly increased in the MI group. The mRNA and protein expressions of collagen type I, collagen type III, TIMP-1 and TGF-beta1 were all decreased by MSC transplantation in our study, although no significant difference was found for the mRNA and protein expressions of MMP-1 between the MI group and the MI+MSC group.


CONCLUSIONS
Our results demonstrated that MSC transplantation could inhibit LV remodeling and improve heart function.
Xu
Xiaohua
X
Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Xu
Zenglu
Z
Xu
Yuanyuan
Y
Cui
Guanghui
G
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D015153:Blotting, Western; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000473:pathology* / Q000628:therapy*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000502:physiology*
D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020781:Matrix Metalloproteinase 1