title: The homing and inhibiting effects of hNSCs-BMP4 on human glioma stem cells.
abstract: Malignant gliomas patients have a poor survival rate, partially due to the inability in delivering therapeutic agents to the tumors, especially to the metastasis of human glioma stem cells (hGSCs). To explore whether the human neural stem cells (hNSCs) with an over-expression of BMP4 (hNSCs-BMP4) can trace and inhibit hGSCs, in this study, we examined the migration of hNSCs to hGSCs using transwell assay in vitro and performed the fluorescent tracer experiment in vivo. We examined the proliferation, differentiation, apoptosis and migration of hGSCs after co-culturing with hNSCs-BMP4 in vitro and tested the tropism and antitumor effects of hNSCs-BMP4 in the established brain xenograft models of hGSCs. We found that hNSCs-BMP4 could secrete BMP4 and trace hGSCs both in vitro and in vivo. When compared to the normal human astrocytes (NHAs) and hNSCs, hNSCs-BMP4 could significantly inhibit the invasive growth of hGSCs, promote their differentiation and apoptosis by activating Smad1/5/8 signaling, and prolong the survival time of the tumor-bearing nude mice. Collectively, this study suggested that hNSCs-BMP4 may help in developing therapeutic approaches for the treatment of human malignant gliomas.
authors.affiliation: Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA.|Departments of Psychiatry and Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.|Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
authors.forename: Ramkrishna
authors.initials: R
authors.lastname: Mitra
authors.affiliation: National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000008:administration & dosage* / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4
keywords: BMP4; homing effects; human glioma stem cells; human neural stem cells; inhibiting effects