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Stem Cells Transl Med ; 6(2): 471-481, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28191774

RESUMEN

Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain. To this end, we discovered a newly described NG2-expressing cell that we isolated from a distinct pericyte subtype found abundantly in cultures derived from peripheral muscle. In this work, we show the translational significance of these peripherally derived neural-like stem cells (NLSC) and their potential to migrate toward tumors and act as therapeutic carriers. We demonstrate that these NLSCs exhibit in vitro and in vivo GBM tropism. Furthermore, NLSCs did not promote angiogenesis or transform into tumor-associated stromal cells, which are concerns raised when using other common stem cells, such as mesenchymal stem cells and induced neural stem cells, as therapeutic carriers. We also demonstrate the potential of NLSCs to express a prototype therapeutic, tumor necrosis factor α-related apoptosis-inducing ligand and kill GBM cells in vitro. These data demonstrate the therapeutic potential of our newly characterized NLSC against GBM. Stem Cells Translational Medicine 2017;6:471-481.


Asunto(s)
Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioblastoma/terapia , Músculo Esquelético/citología , Células-Madre Neurales/trasplante , Pericitos/trasplante , Trasplante de Células Madre/métodos , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Animales , Antígenos/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Diferenciación Celular , Línea Celular Tumoral , Linaje de la Célula , Movimiento Celular , Separación Celular , Técnicas de Cocultivo , Terapia Genética/efectos adversos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Desnudos , Ratones Transgénicos , Neovascularización Fisiológica , Células-Madre Neurales/metabolismo , Pericitos/metabolismo , Fenotipo , Proteoglicanos/metabolismo , Trasplante de Células Madre/efectos adversos , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
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