Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/36352
Title: Human Pluripotent Stem Cell-Derived Cellular Vehicles for Cancer Gene Therapy
Authors: DANG HOANG LAM
Keywords: iPS cells, neural stem cells, cancer gene therapy, tumor tropism, suicide gene therapy, glioblastoma
Issue Date: 16-Aug-2012
Source: DANG HOANG LAM (2012-08-16). Human Pluripotent Stem Cell-Derived Cellular Vehicles for Cancer Gene Therapy. ScholarBank@NUS Repository.
Abstract: Gene therapy coupled with stem cell vehicles to achieve tumor-specific therapeutic effects is a promising treatment for cancer patients. However, one major issue with stem cell based gene therapy is the use of adult stem cells which causes limited cell sources and variable quality. To overcome these obstacles, we propose pluripotent stem cells as alternative cell sources for large-scale production. In this study, we proved that modified human embryonic stem cell (hESC)-derived neural stem cells (NSCs) and mesenchymal stem cells (MSCs) expressing herpes simplex virus-thymidine kinase (HSV-tk) gene noticeably reduced tumor size and improved the survival rate in glioma bearing mice under the systemic administration of ganciclovir (GCV). Similarly, we showed that induced pluripotent stem cell (iPS cell)-derived NSCs also displayed a robust migration towards invasive brain tumor, resulting in a significant tumor regression with HSVtk/GCV system. Using a dual-color imaging technology, we discovered that iPS-NSCs possessed a strong migration towards orthotopic mammary tumors after tail vein injection. Transduced iPS-NSCs with baculoviral vector containing HSVtk gene inhibited the growth and metastasis of breast tumors. Therefore, our study provides evidence supporting the use of pluripotent stem cells as potential alternatives to derive therapeutic cells for cancer treatment.
URI: http://scholarbank.nus.edu.sg/handle/10635/36352
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