The homing and inhibiting effects of hNSCs-BMP4 on human glioma stem cells.
The homing and inhibiting effects of hNSCs-BMP4 on human glioma stem cells.
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hNSCs-BMP4 对人胶质瘤干细胞的归巢和抑制作用。
DOI：
10.18632/oncotarget.7472
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Fan M
中科院分区：
文献类型：
--
作者：
Liu S;Yin F;Zhao M;Zhou C;Ren J;Huang Q;Zhao Z;Mitra R;Fan W;Fan M
恶性神经胶质瘤患者的存活率很低，部分原因是无法将治疗剂递送至肿瘤，特别是人神经胶质瘤干细胞（hGSC）的转移。为探讨BMP 4过表达的人神经干细胞（hNSCs-BMP 4）是否具有示踪和抑制hGSCs的作用，本研究采用transwell法检测hNSCs向hGSCs的迁移，并进行了体内荧光示踪实验。我们在体外检测了hNSCs-BMP 4与hGSCs共培养后的增殖、分化、凋亡和迁移，并在所建立的hGSCs脑异种移植模型中检测了hNSCs-BMP 4的向性和抗肿瘤作用。我们发现hNSCs-BMP 4在体外和体内都能分泌BMP 4和追踪hGSC。与正常人星形胶质细胞（NHAs）和hNSCs相比，hNSCs-BMP 4能显著抑制hGSCs的侵袭性生长，并通过激活Smad 1/5/8信号通路促进其分化和凋亡，延长荷瘤裸鼠的生存时间。总的来说，这项研究表明，hNSCs-BMP 4可能有助于开发治疗人类恶性胶质瘤的治疗方法。
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.