Molecular analysis of the tissue-engineered and regenerated bones using the mesenchymal stem cells and gene-containing carriers

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In order to further analyze the mechanisms and involvement of the cytokine signaling in the bone regeneration, first human keloid-derived fibroblast primary cultures were tested for the' possible resistance against induced apoptosis by ceramide. Ceramide normally induces the fibroblast apoptosis in dose-dependent and in the-dependent Banner; however, fibroblasts derived from keloid showed the G2 arrest by FACS cell sorter and confined by reduced cell number by WST-t assay. When IGF-1 added, keloid fibroblasts resist the ceramide-induced apoptosis. This was positively correlated with IGF-1 receptor expression level. PI-3 inhibitor. Wortmaninn pre-treatment, was markedly abolished inhibition of apoptosis via IGF-1 signaling. In this experiment, the IGF-1 involves in the subsequent signaling via its proper receptor and the molecularly regulated.On the other hand, on behalf of prolonged skin allograft survival, the effective modalities such as cytokine gene therapy were tested. In between BALB/c and B6D2F1 strain mice Leukemia Inhibitory Factor, LIF plasmid CDNA was injected into the skin allograft donor, LIF expressions were observed in 24 hours and 21 days post-transplantation. The gp130, signal-transduction component of LIF, was expressed along with LIF. When B6D2F1 to BALB/c skin allograftIng, helper T type2 cytokine (IL-10) was observed, thus immune tolerance was indicated for skin allografting in LIF gene therapy.In bone metabolism, LIF was tested in the cranial bone defect model. LIF was efficiently enhanced the bone formation via osteocyte activation. In combined use of the osteogenic cytokioea (bFGF and BMP-2) and human mesenchymal stem cells in the cranial bone defects demonstrated the significant boneregeneration with sponge carriers underneath.