NOVEL PERIPHERALLY DERIVED NEURAL-LIKE STEM CELLS AS DRUG DELIVERY VEHICLES FOR GLIOBLASTOMA
Glioblastoma (GBM) is an aggressive primary malignant astrocytoma characterized by infiltrating margins and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be partially effective in treating GBM and its recurrence. Stem cells have been shown to migrate to tumor sites when transplanted loco-regionally into the brain and their role in the initiation and maintenance of tumors in various organs, including GBM has been evidenced. Due to their tumor trophic behavior, stem cells are being aggressively researched as drug delivery vehicles for cancer therapy. Mesenchymal Stem Cells, induced Pluripotent Stem Cells and other peripherally derived stem cells (commonly used against GBM) have been shown to promote angiogenesis and transform into tumor associated stromal cells upon transplantation in vivo. Peripherally derived neural like stem cells (NLSCs), discovered recently by our group, showed GBM-tropism in vitro and in vivo. NLSCs did not form tumors when transplanted subcutaneously or intra-cranially for many months (>5 months). Importantly, NLSCs showed a significant advantage over other commonly used peripherally derived stem cells as they did not promote angiogenesis when cultured with HUVECs and did not transform into tumor associated stromal cells when exposed to TGF-β. When genetically engineered, NLSCs successfully secreted TRAIL, a prototype therapeutic and showed GBM cell killing in vitro. Thus, we had demonstrated our NLSCs to be effective delivery vehicles for anti-GBM therapeutics.
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