Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair

Ying Dai, Muhammad Ashraf, Shi Zuo, Ryota Uemura, Yan Shan Dai, Yigang Wang, Husnain Kh Haider, Tingyu Li, Meifeng Xu

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

We proposed here that mobilized progenitor cells (MPCs) from the bone marrow are special cell types which carry cytoprotective proteins for cardiac repair following ischemia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery (LAD) in mice. Progenitor cells in peripheral blood were analyzed by fluorescence-activated cell sorting (FACS). The expression of cytoprotective genes was assayed by ELISA, RT-PCR, and/or real-time PCR. G-CSF was markedly up-regulated in the ischemic myocardium. A good correlation was observed between serum G-CSF and progenitor cells in circulation following LAD ligation. MPCs overexpressed cardiac transcription factor, GATA-4, and anti-apoptotic factor, Bcl-2, besides expression of the surface markers of bone marrow stem cells (BMSCs). Transplantation of cultured MPCs into the ischemic border area significantly improved cardiac function by reducing infarction size. More importantly, MPCs significantly protected cardiomyocytes against apoptosis when co-cultured with cardiomyocytes. The cardiac protection by MPCs was blocked by Bcl-2 neutralizing antibody and GATA-4 siRNA. In contrast, transfection of BMSCs with GATA-4 provided increased protection of myocytes against apoptosis. It is concluded that MPCs are highly cytoprotective and carry protective genes responsible for cardiac repair.

Original languageEnglish (US)
Pages (from-to)607-617
Number of pages11
JournalJournal of molecular and cellular cardiology
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 1 2008
Externally publishedYes

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Keywords

  • BMSCs
  • Bcl-2
  • Cytoprotective protein
  • G-CSF
  • GATA-4
  • Ischemia
  • Mobilization
  • Progenitor cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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