The homing and inhibiting effects of hNSCs-BMP4 on human glioma stem cells

// Shuang Liu 1, * , Feng Yin 1, * , Mingming Zhao 1 , Chunhui Zhou 1 , Junlin Ren 1 , Qiming Huang 2 , Zhongming Zhao 3, 4, 5 , Ramkrishna Mitra 3 , Wenhong Fan 6 , Ming Fan 2 1 Department of Neurosurgery, Navy General Hospital, PLA, Beijing 100048, China 2 Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing 100850, China 3 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA 4 Departments of Psychiatry and Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA 5 Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA 6 National Institutes for Food and Drug Control, Beijing 100050, China * These authors have contributed equally to this work Correspondence to: Shuang Liu, e-mail: shuangff@sina.com Ming Fan, e-mail: fanmingchina@126.com Keywords: human glioma stem cells, human neural stem cells, BMP4, homing effects, inhibiting effects Received: September 22, 2015      Accepted: February 11, 2016      Published: February 18, 2016 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.