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

描述（由申请人提供）：GBMs是迅速致命的，仅在美国每年就有近14,000名患者死亡。这项提议的目标是治疗性地利用新分离的神经样干细胞（NLSCs）纯群体，我们最近从周细胞中获得，因此可能成为自体移植的潜在来源。我们申请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生产一种新型高毒性靶向细菌细胞毒素。待验证的中心假设是，我们可以利用图像引导的HIFU以一种创新的方式利用NLSCs，在我们选择的深度轻度加热肿瘤组织，并诱导一种由热休克蛋白70启动子（pHSP70）控制的新型治疗生产。为了验证这一假设，将实现两个特定目标：（特定目标1）证明外周分离NLSCs的肿瘤亲和性和安全性。（特定目标2）为了证明使用图像引导的HIFU远程激活诱导TQM13-CTX的可行性，一种新的靶向抗GBM治疗方法，靶向肿瘤限制性IL13R。使用新的基于干细胞的治疗方法将治疗剂特异性地传递到肿瘤细胞而不是周围的正常脑组织，为治疗GBM（一种不可避免的致命疾病）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.