Increased heme oxygenase-1 expression in infarcted rat hearts following human bone marrow mesenchymal cell transplantation

Microvasc Res. 2005 Jan;69(1-2):64-70. doi: 10.1016/j.mvr.2005.01.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Bone Marrow Cells / cytology*
  • Cells, Cultured
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1
  • Humans
  • Male
  • Membrane Proteins
  • Mesenchymal Stem Cell Transplantation*
  • Middle Aged
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Transplantation, Heterologous

Substances

  • Membrane Proteins
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1