Htrail Genetically Modified Bone Marrow Stromal Stem Cell Targeting Of Glioma Gene Therapy Research

Malignant glioma was the commonest primary tumor in central neural system. They are aggressive, highly invasive, and extensively infiltrative. The prognosis of patients with malignant gliomas, such as glioblastoma multiforme or anaplastic astrocytoma, is extremely poor, despite their extensive surgical treatment and adjuvant radio- and chemotherapy. Since last 90 's, the tide of gene therapy have cast light on the therapy of malignant glioma, which was behaved by HSV-Tk/GCV "suicide gene" system. However, the results from phase I and II clinical trial were disappointed, which may due to the instability of virus vector, short-term expression of targeted genes, lack of tumor al targeting, immunogenicity of virus, and incapability to tracking infiltrative glioma cells, mesenchymal stem cells (MSCs) can migrated to glioma cells, and TNF-related apoptosis-inducing ligand (TRAIL) can induce cancer cells into apoptosis exclusively. Based on these findings, we combined the two targeting mechanism to explore the feasibility of targeted glioma therapy with the TRAIL modified MSCs.Firstly, we isolated the adult human MSCs by gradient centrifuge with 1.073 1.073g/ml Percoll. After expansion in vitro, they developed into fibroblast-like cells, which expressed CD105, CD166 and CD44, but not CD1 lb, CD34 and CD45. Moreover, they can differentiated into Osteoblast, adipocyte, and chondrocyte when cultured with conditional media.Further to investigate the glioma tropism capacity of MSCs, GFP labeled MSCs were cocultured with U87MG glioma cells. The hMSCs migrated toward U87MG clones and clustered around the clones, whereas no green MSCs could be seen in any other place. Transwell assay found conditioned media from U87MG cells, U87MG cells, and lysis of U87MG glioma significantly stimulated the directional migration of the MSCs compared to lysis of normal brain tissue (*p<0.05, t test). In addition, the response of NIH3T3 cells in migration capacity was no significantly different under the stimulus, ntravenously injection of LacZ labeled MSCs into the mice with the intracranial U87MG glioma, blue MSCs distributed into glima. LacZ positive MSCs in glioma were much more than other place...