Organoids Derived From Induced-Pluripotent Stem Cells (iPS) From Patients With High Grade Astrocytoma

Study Overview
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Brief Summary
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The objective of this study research proposal is to model human gliomagenesis using 3-Dimensional (3D) brain organoids derived from human induced pluripotent stem cells (hiPSCs). The working hypothesis is that 3D brain organoids can develop glioma-like structures and recapitulate phenotypic traits of gliomas when generated from hiPSCs expressing genetic mutants associated with glioma predisposition. Methodology : To develop this pioneer study on the use of hiPSC-based brain organoids as a strategy to model gliomagenesis and study the impact of genetic mutants, it will be collect the peripheral blood mononuclear cell from 20 patients with high grade astrocytoma with or without IDH mutation. iPS will be generated from these PBMC and will be genetically modified according to different mutations. Then, it will be generate brain organoids according to standard protocols. Brain organoids generated from all different cells will be collected at different time points and analyzed for the presence of glioma-like structures and phenotypic hallmarks of gliomas. From the proposed experiments, it will be expect that brain organoids will develop glioma-like features upon the presence of genetic mutations. Thus, it will be expect to demonstrate that brain organoids can be used as a reliable strategy to test the impact of genetic mutants, including the possible synergistic cooperation between different mutations on early gliomagenic events.

Official Title
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Organoids Derived From Induced-Pluripotent Stem Cells (iPS) From Patients

Conditions
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Glioma

Intervention / Treatment
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* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient, male or female, aged 18 years or older Astrocytoma grades 3 or 4, confirmed by anatomopathological diagnosis Patient having signed an informed consent Exclusion Criteria: Person in emergency situation, a legal person of legal age (guardianship, guardianship or legal guardianship), or unable to express his / her consent No affiliation to a social security scheme (beneficiary or beneficiary) Pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient with high grade astrocytoma<br>Patients meeting inclusion and non-inclusion criteria and having signed informed consent will be included in the study | Biological: Blood sample<br>* A blood sample of two 10 mL ethylenediaminetetraacetic (EDTA) tubes will be taken at the time of the visit. This sample will be centrifuged for isolation of peripheral blood mononuclear cells (PBMC).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the level of proliferation of organoids | compare different immunohistochemical markings between organoids | 18 months |