Primary neural stem/progenitor cells expressing endostatin or cytochrome P450 for gene therapy of glioblastoma

Cancer Gene Therapy
A LoricoG Rappa

Abstract

Despite recent technical improvements in surgical excision techniques and adjuvant radio- and chemotherapy, the clinical outcome of patients with grade IV astrocytoma (glioblastoma) remains very poor, with a median survival of less than 12 months. A promising approach to therapy employs gene-engineered neural stem/progenitor cells (NSCs) as a cellular therapeutic delivery system, to track glioblastoma cells and deliver anticancer molecules. However, most results on their tumor tropism have been derived by immortalized NSCs. We now report that primary murine gene-engineered NSCs displayed in vivo tropism for glioblastoma cells. Ten days after injection into the brain, many NSCs continued to express the transgene and the NSC marker, nestin. NSCs transduced with a retroviral vector co-expressing a secretable form of human endostatin and eGFP (NSC/endo-eGFP) released potentially antiangiogenetic concentrations of endostatin into the culture medium. Conditioned medium of NSC/endo-eGFP cells inhibited the growth of mouse pulmonary microvascular endothelial cells (PMVECs). A good correlation between endostatin levels and PMVEC growth inhibition was observed. In NSCs co-expressing cytochrome P450 2B6 (CYP2B6) and eGFP (NSC/CYP2B6-eGFP)...Continue Reading

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Citations

Jul 16, 2011·Molecular Pharmaceutics·Esther Xingwei LeeShu Wang
Mar 25, 2011·Human Molecular Genetics·William J BowersMiguel Sena-Esteves
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Aug 5, 2009·International Journal of Cancer. Journal International Du Cancer·Javier MercapideAurelio Lorico
Nov 10, 2013·Cancers·Aneta KwiatkowskaMariano S Viapiano
Sep 2, 2014·International Journal of Molecular Medicine·Javier Mercapide, Aurelio Lorico
Feb 13, 2016·Oncology Letters·Hiroki NambaTomohiro Yamasaki

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