hMSC-mediated Concurrent Delivery of Endostatin and Carboxylesterase to Mouse Xenografts Suppresses Glioma Initiation and Recurrence
| Autor: | Sung Hak Kim, Xun Jin, Yun-Jaie Choi, Hyunggee Kim, Do-Hyun Nam, Seungkwon You, Young Chang Lim, Da-Chuan Piao, Jai Hee Moon, Samuel Beck, Jinlong Yin, Jun Kyum Kim |
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| Rok vydání: | 2011 |
| Předmět: |
Angiogenesis
Population Brain tumor Mice Nude Biology Carboxylesterase Mice Cell Line Tumor Glioma Drug Discovery medicine Genetics Animals Humans education Molecular Biology Pharmacology education.field_of_study Reverse Transcriptase Polymerase Chain Reaction Mesenchymal stem cell Mesenchymal Stem Cells medicine.disease Xenograft Model Antitumor Assays Endostatins Cell culture Cancer research Molecular Medicine Original Article Stem cell Endostatin |
| Zdroj: | Molecular Therapy. 19(6):1161-1169 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2011.28 |
| Popis: | Glioma stem cells (GSCs) are known to be maintained within a "vascular niche"; thereby, disruption of this microenvironment using antiangiogenesis agents is a promising therapeutic modality. However, this regimen leads to treatment failure and tumor recurrence in patients with glioblastoma multiforme (GBM). Therefore, more effective therapeutic approaches that can eradicate GSCs and the bulk tumors are needed. Toward this goal, we examined the antitumor effects of an antiangiogenesis approach combined with conventional chemotherapy on suppressing glioma xenograft growth. We established three genetically engineered mesenchymal stem cell (MSC) lines (GE-AF-MSCs) by stably transducing the gene encoding endostatin (an antiangiogenesis factor), the gene encoding secretable form of carboxylesterase 2 (sCE2, a prodrug-activating enzyme), or a mixture of both genes. Among the three GE-AF-MSC cell lines, injection of amniotic fluid (AF)-MSCs-endostatin-sCE2 cells into U87MG-EGFRvIII-driven orthotopic brain tumor and postsurgery tumor recurrence models, and subsequent CPT11 treatment yielded the strongest antitumor responses, including diminished angiogenesis, increased cell death, and a reduced Nestin-positive GSC population. Therefore, our antitumor strategy provides a novel basis for designing stem cell-mediated therapeutic approaches to target and eradicate GSCs and the bulk tumors. |
| Databáze: | OpenAIRE |
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