PRECLINICAL STUDY OF HEMATOPOIETIC SYSTEM REGENERATION FOLLOWING EXPOSURE TO GENOTOXIC STRESS SUCH AS IRRADIATION AND CHEMOTHERAPY (ALL/AML)
- Preclinical development
- ALL
- AML
- Targeted therapy
- Chemotherapy
- Preclinical research (TRL 4-5)
Study of the regeneration of the human hematopoietic system following exposure to genotoxic stress such as irradiation and chemotherapy.
The models developed accurately represent the biology and heterogeneity of normal hematopoietic cells and recapitulate the normal bone marrow microenvironment.
Description
Scope of research activities
Preclinical research to monitor hematopoietic development:
- Monitoring the development of human hematopoiesis
- Monitoring the impact of preclinical molecules on the human bone marrow niche using an in vivo humanized bonelet model in immunodeficient mice
Conduc of studies
Steps:
- Analysis of innovative product development strategy
- Study design
- Drafting of study plans
- Establishment of quotes to finance the study
- Organization, implementation and conduct of studies
- Analysis and communication of results
Research infrastructure
Experimental and analytical platforms:
- Flow cytometry
- Animal experimentation (dedicated personnel)
- Animal facility
- Molecular bioengineering (dedicated personnel)
- Microscopy
- Immunohistochemistry and immunoflurescence on sections
Preclinical models:
- Immunodeficient mice with human chimerism
- Immunodeficient mice with human ossicles: analysis of non-hematopoietic cells in the bone niche
Specifications
The platform
Set of studies to measure hematopoiesis regeneration using in vitro assays and/or chimeric immunodeficient mice irradiated or treated with chemotherapy.
The studies
Assessment of molecule toxicity on normal human hematopoietic development:
- Hematopoietic development in the bone marrow of immunodeficient mice: flow cytometry monitoring of human cells and the level/quality of human chimerism
Evaluation of the efficacy of drug candidates in vitro on differentiating human hematopoietic cells:
- Monitoring of lymphoid, myeloid and/or erythroid cell production in vitro; testing of molecules: apoptotic effect/cell death, growth alteration
Evaluation of the efficacy of drug candidates on the hematopoietic stem/progenitor cell (HSPC) compartment:
- Treatment of HSPCs in vivo or in vitro; testing of multilineage hematopoietic reconstitution in vivo after transplantation or in vitro in functional assays (CFC, LTC-IC)
Evaluation of the efficacy of drug candidates on the regeneration of human hematopoiesis in vivo and/or in vitro after treatment (chemotherapy, irradiation):
- Treatment of humanized mice in vivo; monitoring of hematopoietic regeneration in vivo after treatment
Examples of partnerships
Study of the efficacy of the G-CSF and Plerixafor combination on the mobilization of stem/progenitor cells from poorly mobilizing patients - The aim was to study the multi-lineage hematopoietic reconstitution functions of HSPCs mobilized in patients with the G-CSF and Plerixafor combination by transplantation into immunodeficient mice.
Partner: Institut Gustave Roussy (Prof. J-H Bourhis, Dr. S Amsellem)
Study of the effects of ultra-high dose rate irradiation on T-ALL and human hematopoiesis - This involved a comparative study of the effect of a given dose of Flash (high dose rate) and conventional (low dose rate) irradiation on leukemic development and normal hematopoiesis, in vivo in humanized mice.
Partners: Center Hospitalier Universitaire Vaudois (CHUV), University of Lausanne (Dr. M-C Vozenin)
Terms
OPALE entity
UMR - 1274
Head of Entity
Contact
Dr. Sandrine PalcyBusiness Development Director