Abstract 13: Overexpression of FABP3 Inhibits Human Bone Marrow Derived Mesenchymal Stem Cell Proliferation but Enhances Their Survival in Hypoxia
Background: Studying the proliferative ability of human bone marrow derived mesenchymal stem cells (MSC) in hypoxic conditions provides and understanding of their regenerative capacity in ischemic myocardium. FABP3 is a specific marker of myocardial injury and may be responsible for the modulation of cell proliferation and differentiation.
Methods: MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions. Following this treatment, gene expression patterns and further gene functional based studies such as comparative semi-qPCR, cell growth/proliferation analysis and Western blotting analysis were performed.
Results: We identified: 1) the FABP3 differential expression pattern in the MSCs under hypoxic condition; 2) over-expression of FABP3 by lentiviral transduction in MSCs (MSCFABP3LV) inhibited cell growth and proliferation but significantly enhanced the cells survival in a low oxygen environment and 3) the following cell growth factors and cell cycle M phase key genes IGF, PCNA, APC, CCNB1, CCNB2, CDK1and CDC20 were all down-regulated in the FABP3-overexpressing cells; however, the key negative regulation of cell cycle genes BRCA1, CASP3 and TP53 were significantly overexpressed in the MSCFABP3LV compared to control groups. These data suggested that FABP3 inhibits cells in the mitosis phase.
Conclusions: FABP3 is a hypoxic target in human MSCs. Overexpression of FABP3 inhibits cell growth and proliferation via negative regulation of the cell cycle and down regulation of cell growth factors but provides stabilization of the cells for survival in hypoxic or ischemic condition.
- © 2013 by American Heart Association, Inc.