Mesenchymal Stem Cells as Cellular Vehicles Encapsulate Therapeutic Retroviruses Against Gliomas

碩士 === 國立中正大學 === 分子生物研究所 === 102 === Although conventional therapies for malignant glioma such as surgical resection, radiotherapy and chemotherapy are available, the prognosis for patients with this disease remains extremely poor. Glioma has an exceptional infiltrative potential and integrate into...

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Bibliographic Details
Main Authors: Yu-Hsuan Yang, 楊宇軒
Other Authors: Chien - Kuo Tai
Format: Others
Language:zh-TW
Published: 2013
Online Access:http://ndltd.ncl.edu.tw/handle/45009272441053537525
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Summary:碩士 === 國立中正大學 === 分子生物研究所 === 102 === Although conventional therapies for malignant glioma such as surgical resection, radiotherapy and chemotherapy are available, the prognosis for patients with this disease remains extremely poor. Glioma has an exceptional infiltrative potential and integrate into abutting tissue, therefore, it is hard to completely cure glioma. Recently, mesenchymal stem cells (MSC) have been found possessing inherent tumor tropic properties and offering much promise as delivery vehicles for brain tumor therapy. We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of rat adipose-derived MSC (A-MSC) expressing cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatments. Co-culture of rat glioma cells (RG2) with A-MSC-CD conditioned media which contain 5-FU converted from 5-FC resulted in a remarkable reduction in cell viability. The migratory ability of A-MSC toward glioma cells was demonstrated by transwell assay. We have also infected rat bone marrow-derived MSC (BM-MSC) with replicating retrovirus vector (RRV) developed in our lab. The result showed that RRV released from BM-MSC could further infect glioma cells, achieving persistent gene delivery to gliomas in vitro and in vivo. In the future we will exam the therapeutic effects of such MSCs in an orthotopic mouse model of human glioma. We wish the use of BM-MSC as the vehicle for dispersing RRV may provide a viable strategy for delivering a therapeutic payload to disseminated glioma burdens.