Accurate pre-clinical models of human cancer are essential for basic and translational research. The undeniable necessity of such models clashes with the reality of their ineffectiveness to replicate the context where human tumors form. Here is presented a new mouse model for human Medulloblastoma (MB) disease, a pediatric brain tumor with high incidence and frequent lethal recurrencies, for which conventional treatments often cause lifelong drawbacks. By leveraging the “immune-privileged” embryonic developmental time window, orthotopic xenotransplantation of human MB cells were successfully engrafted in immune-competent mice. The xenotransplants integrated into the host brain, reconstituting several tumor microenvironment characteristics by demonstrating infiltration, vascularization, and immune cell infiltration. Second, aimed to respond to the urgencies of new therapies, the MB model was here used to assess the efficacy of a pool of 11 microRNAs (miRNAs) that has been previously described to induce neuro-differentiation in neural progenitor populations. Non-coding RNAs play a fundamental role in cancer, with miRNAs occupying the frontlines being capable of either hijack or suppress tumor biology. Effective therapies cannot be devised if developed within a flawed system. We find that the engrafted MB tumors are responsive to the 11-miRNA pool pre-treatment, exhibiting reduced tumor proliferation and infiltrative-like features. The approach here described enables the study of human MB formation and biology under conditions resembling its physiopathology, specifically in an embryonic and immune-competent environment. This mouse model can serve as platform to study efficacy of therapies, here demonstrated by means of miRNAs, offering significant opportunities for neuro-oncological research.

A novel immune-competent murine model to evaluate the efficacy of a microRNA-based therapy for the pediatric brain tumor Medulloblastoma

LA ROSA, LETIZIA
2024-02-28

Abstract

Accurate pre-clinical models of human cancer are essential for basic and translational research. The undeniable necessity of such models clashes with the reality of their ineffectiveness to replicate the context where human tumors form. Here is presented a new mouse model for human Medulloblastoma (MB) disease, a pediatric brain tumor with high incidence and frequent lethal recurrencies, for which conventional treatments often cause lifelong drawbacks. By leveraging the “immune-privileged” embryonic developmental time window, orthotopic xenotransplantation of human MB cells were successfully engrafted in immune-competent mice. The xenotransplants integrated into the host brain, reconstituting several tumor microenvironment characteristics by demonstrating infiltration, vascularization, and immune cell infiltration. Second, aimed to respond to the urgencies of new therapies, the MB model was here used to assess the efficacy of a pool of 11 microRNAs (miRNAs) that has been previously described to induce neuro-differentiation in neural progenitor populations. Non-coding RNAs play a fundamental role in cancer, with miRNAs occupying the frontlines being capable of either hijack or suppress tumor biology. Effective therapies cannot be devised if developed within a flawed system. We find that the engrafted MB tumors are responsive to the 11-miRNA pool pre-treatment, exhibiting reduced tumor proliferation and infiltrative-like features. The approach here described enables the study of human MB formation and biology under conditions resembling its physiopathology, specifically in an embryonic and immune-competent environment. This mouse model can serve as platform to study efficacy of therapies, here demonstrated by means of miRNAs, offering significant opportunities for neuro-oncological research.
28-feb-2024
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1163019
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