Therapeutically Exploiting a Newly Isolated Neural-Like Stem Cell Against GSB

描述(由申请人提供)：GBM是迅速致命的，仅在美国每年就导致近14,000名患者死亡。这项提议的目标是从治疗上利用我们最近从周细胞中分离出来的新分离的神经样干细胞(NLSCs)，因此可能成为自体移植的来源。我们的应用程序的目标是使用一种创新的远程可控干细胞平台，使我们能够在我们选择的时间和地点非侵入性地激活NLSC生产一种新型的高毒性靶向细菌细胞毒素。需要测试的中心假设是，我们可以使用图像引导的HIFU以创新的方式利用我们的NLSCs来温和加热我们选择的深度的肿瘤组织，并诱导由热休克蛋白70启动子(PHSP70)控制的新的治疗产物。为了验证这一假设，将执行两个特定目标：(特定目标1)证明外周分离的NLSCs的肿瘤趋向性和安全性。(特定目的2)为了证明使用图像引导的高强度聚焦超声远程激活来诱导TQM13-CTX的可行性，一种新型的靶向抗基底细胞瘤疗法，它针对肿瘤限制性的IL13R�递送治疗药物，特异性地针对肿瘤细胞，而不是周围的正常脑组织，使用基于干细胞的新型疗法提供了对抗基底膜的希望，基底膜是一种总是致命的疾病。因此，这一建议具有很强的翻译相关性。

DESCRIPTION (provided by applicant): GBMs are rapidly fatal and kill close to 14,000 patients annually in the US alone. The goal of this proposal is to therapeutically exploit a newly isolated pure population of neural-like stem cells (NLSCs) that we recently derived from pericytes and can thus potentially be a source of autologous transplantation. The objectives of our application are to use an innovative remote-controllable stem cell-based platform to allow us to non-invasively activate NLSC production of a novel highly toxic targeted bacterial cytotoxin at the time and place of our choosing. The central hypothesis to be tested is that we can therapeutically exploit our NLSCs using image-guided HIFU in an innovative way to mildly heat tumor tissue at the depth of our choosing and induce a novel therapeutic production controlled by the heat shock protein 70 promoter (pHSP70). To test this hypothesis, 2 specific aims will be performed: (Specific Aim 1) To demonstrate tumor tropism and safety of peripherally isolated NLSCs. (Specific Aim 2) To demonstrate the feasibility of using image-guided HIFU remote activation to induce a TQM13-CTX, a novel targeted anti-GBM therapeutic that targets the tumor-restricted IL13R� Delivery of therapeutic agents specifically to tumor cells but not to the surrounding normal brain tissue using novel stem cell-based therapies offers hope against GBM, an invariably fatal disease. Thus, this proposal has strong translational relevance.