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.
High grade malignant gliomas are the leading cause of primary brain cancer deaths, afflicting close to 20,000 patients annually in the United States alone. We are proposing to create an innovative, clinically relevant anti-tumor strategy using novel stem cells and remote controlled therapeutic activation with potential to eradicate infiltrating tumor cells and prevent brain tumor recurrence while causing no collateral damage to normal brain. Our approach promises to significantly improve therapy against malignant brain cancers.
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| Prazeres, Pedro H D M; Turquetti, Anaelise O M; Azevedo, Patrick O et al. (2018) Perivascular cell ?v integrins as a target to treat skeletal muscle fibrosis. Int J Biochem Cell Biol 99:109-113 |
| Prazeres, Pedro H D M; Almeida, Viviani M; Lousado, Luiza et al. (2018) Macrophages Generate Pericytes in the Developing Brain. Cell Mol Neurobiol 38:777-782 |
| Costa, Matheus A; Paiva, Ana E; Andreotti, Julia P et al. (2018) Pericytes constrict blood vessels after myocardial ischemia. J Mol Cell Cardiol 116:1-4 |
| Silva, Walison N; Prazeres, Pedro H D M; Paiva, Ana E et al. (2018) Macrophage-derived GPNMB accelerates skin healing. Exp Dermatol 27:630-635 |
| Silva, Walison N; Leonel, Caroline; Prazeres, Pedro H D M et al. (2018) Role of Schwann cells in cutaneous wound healing. Wound Repair Regen 26:392-397 |
| Paiva, Ana E; Lousado, Luiza; Guerra, Daniel A P et al. (2018) Pericytes in the Premetastatic Niche. Cancer Res 78:2779-2786 |
| Guerra, Daniel A P; Paiva, Ana E; Sena, Isadora F G et al. (2018) Adipocytes role in the bone marrow niche. Cytometry A 93:167-171 |
| Guerra, Daniel A P; Paiva, Ana E; Sena, Isadora F G et al. (2018) Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome. Angiogenesis : |
| Santos, G S P; Prazeres, P H D M; Mintz, A et al. (2018) Role of pericytes in the retina. Eye (Lond) 32:483-486 |
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