Novel Peripherally Derived Neural-Like Stem Cells as Therapeutic Carriers for Treating Glioblastomas

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 tomigratetowardtumorsandactastherapeuticcarriers.WedemonstratethattheseNLSCsexhibit 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 a-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 2016;5:1–11 SIGNIFICANCE Radiation and chemotherapy have failed to cause significant therapeutic benefit in glioblastoma patients because of their limitations. This has spurred investigations into the use of engineered stem cellstodeliverantitumordrugsasacomplementarystrategy.Thisstudyreportsthatneural-likestem cellsisolatedfromskeletalmusclesshowtumor-tropismandcanbeengineeredtosecretetherapeuticsbutdonotformtumorsanddonottransformintotumor-associatedcellsorcauseangiogenesis, incontrasttocommonlyusedstemcells.Theseadvantagescoupledwiththetherapeuticpotentialof neural-like stemcellshighlights their abilityto be used as therapeutic carriersagainst glioblastomas.