title: Novel Peripherally Derived Neural-Like Stem Cells as Therapeutic Carriers for Treating Glioblastomas.
abstract: 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.
authors.affiliation: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Pathology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors.forename: Alexander
authors.initials: A
authors.lastname: Birbrair
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Brain Tumor Center of Excellence, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Anirudh
authors.initials: A
authors.lastname: Sattiraju
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Dongqin
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Zulato
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Izadora
authors.initials: I
authors.lastname: Batista
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Van T
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Messi
authors.affiliation: Brain Tumor Center of Excellence, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Solingapuram Sai
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Delbono
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Brain Tumor Center of Excellence, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002465:Cell Movement; D002469:Cell Separation; D018920:Coculture Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology*; D018919:Neovascularization, Physiologic; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D020286:Pericytes / Q000378:metabolism / Q000637:transplantation*; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: Cellular therapy; Glioblastoma; Muscle stem cells; Neural differentiation; Neural-like stem cells