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

描述（由申请人提供）：GBM具有快速致死性，仅在美国每年就有近14，000例患者死亡。该提案的目标是在治疗上利用一种新分离的纯神经样干细胞（NLSC）群体，我们最近从周细胞中获得，因此可能成为自体移植的来源。我们申请的目的是使用一种创新的基于干细胞的远程可控平台，使我们能够在我们选择的时间和地点非侵入性地激活NLSC生产新型高毒性靶向细菌细胞毒素。待测试的中心假设是，我们可以使用图像引导的HIFU以创新的方式在治疗上利用我们的NLSC，以在我们选择的深度温和地加热肿瘤组织，并诱导由热休克蛋白70启动子（pHSP 70）控制的新型治疗产物。为了检验这一假设，将进行2个具体目标：（具体目标1）证明外周分离的NLSC的肿瘤嗜性和安全性。（具体目的2）为了证明使用图像引导的HIFU远程激活来诱导TQM 13-CTX的可行性，TQM 13-CTX是一种新型靶向抗GBM治疗剂，其靶向肿瘤限制性IL 13 R，使用基于干细胞的新型疗法将治疗剂特异性地递送至肿瘤细胞而不是周围正常脑组织，为对抗GBM（一种总是致命的疾病）提供了希望。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.