Increased heme oxygenase-1 expression in infarcted rat hearts following human bone marrow mesenchymal cell transplantation.
Heme oxygenase-1 (HO-1) plays an important role in oxidative stress and recent studies indicate that it is a graft survival protein in cardiac and liver transplant models. In this study, we investigated the relation between the expressions of HO-1 and the effects of human bone marrow mesenchymal cells (MSCs) transplantation to xenogenic rat hearts with experimental myocardial infarction (MI). A total of 5 x 10(6) cells in 100 microl PBS or equal volume PBS alone were injected into the ischemic zones immediately post-MI. At 1, 3, and 7 days post-MI, cardiac function was evaluated by echocardiography, the expression of HO-1 was assessed by real-time PCR and Western blot, the localization of HO-1 protein was determined under immunofluorescence microscopy. The infarct size was examined by histology. The numbers of Hoechst-33342 positive MSCs were evaluated under immunofluorescence microscopy and also by flow cytometry after isolation from the host hearts. The results indicated that the HO-1 expressions were markedly increased at both mRNA and protein levels in comparison with injection of PBS at each time point post MSCs transplantation (P < 0.01). HO-1 was revealed both in transplanted MSCs and recipient cardiomyocytes by immunofluorescence. Up-regulated HO-1 expression was accompanied by increase of the numbers of Hoechst-33342 positive MSCs, the reduction of infarct size, and the improvement of cardiac function. Transplantation of human MSCs could up-regulate HO-1 expression in infarct rat hearts, which might play an important role in protecting transplanted MSCs, cardiomyocytes survival, and cardiac function improvement during the early stage after MI.
Zhang
Shaoheng
S
Department of Cardiology, The Third Hospital of Peking University, Beijing, China.
Lu
Shun
S
Ge
Junbo
J
Guo
Jingxuan
J
Chen
Ping
P
Li
Tao
T
Zhang
Ping
P
Jia
Zhuqing
Z
Ma
Kangtao
K
Liu
Yonggang
Y
Zhou
Chunyan
C
Li
Linsong
L
D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002478:Cells, Cultured; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1