Molecular tissue engineering: applications for modulation of mesenchymal stem cells proliferation by transforming growth factor beta 1 gene transfer.

Abstract

The effect of transforming growth factor beta 1 (TGF-beta 1) gene transfection on the proliferation of bone marrow-derived mesenchymal stem cells (MSCs) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF-beta 1 gene at different doses was transduced into the rat bone marrow-derived MSCs to examine the effects of TGF-beta 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 microliters lipofectamine-mediated 1 microgram TGF-beta 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine = 1 microgram/3 microliters), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF-beta 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.