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

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

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.

Study Overview

• Status: Unknown
• Conditions: Glioma
• Intervention / Treatment: Biological: Blood sample

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Dominique FIGARELLA, PUPH; Phone Number: +33 413429011; Email: dominique.figarella-branger@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • Assistance Publique Hopitaux de Marseille
    • Principal Investigator: Emeline TABOURET

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients managed for a brain tumor for whom a blood sample collected routinely will be recovered

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient with high grade astrocytoma; Patients meeting inclusion and non-inclusion criteria and having signed informed consent will be included in the study	Biological: Blood sample; 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).

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 7, 2019
• Primary Completion (ANTICIPATED): December 6, 2020
• Study Completion (ANTICIPATED): December 6, 2020

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (ACTUAL): June 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2019-01 (Other Identifier: NANT); 2019-A00145-52 (OTHER: ID RCB number); RCAPHM19_0001 (OTHER: AP-HM secondary number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No