Generation of hematopoietic stem cells hIPSc for treatment of acute irradiation syndrome an innovative therapeutic strategy of hematopoietic syndrome – RESCUE
The objective of the RESCUE project is to propose a new treatment for acute radiation syndrome (ARS) for the military personnel in operation who are victims of nuclear exposure, or for the public who are victims of malevolent acts. It is based on a breakthrough technology to produce hematopoietic stem cells (HSCs) capable of multi-lineage graft obtained from induced pluripotent stem cells reprogrammed from differentiated adult human cells. These original cells are called hiPSC (human induced Pluripotent Stem Cells). hIPSC have begun to revolutionize medical practices.
The emergency treatment of populations requires the availability of ready-to-use frozen products to treat a large group of individuals. Drug" stem cell banks obtained from clinical grade hiPSCs will make it possible to produce stem cells of different types to treat the population. HiPSCs from these "universal" donors are already available in Europe. The RESCUE project aims to demonstrate that this strategy of using hiPSC to produce HSCs is the therapeutic response to the treatment of ARS. This project is in synergy with the new global strategies in terms of health and regenerative medicine, namely the creation of clinical grade hiPSC banks and the derivation of quality cellular products.
The previous GIPSIS project (Astrid 2013-17), is a world first to demonstrate the generation of a long-term functional hematopoietic tissue from hiPSC. We have developed a cGMP (xeno-free) protocol for producing HSC from hiPSC. The reproducibility of this protocol has been demonstrated with 5 different hiPSC lines from 3 healthy donors and 2 leukemic donors. In addition, by selecting 2 surface markers, we are able to enrich our cell population containing HSCs capable of reconstituting functional hematopoiesis. These results are submitted to the prestigious journal Cell.
The RESCUE project aims to demonstrate that this innovative therapy is applicable to a man developing an ARS. We will demonstrate this by validating this treatment in a "large" animal model developing hematopoietic syndrome. This will allow us to progress to a TRL of 6. In order to have a cell therapy product that can be used in clinics, we adopt the approach of validating a human HSC graft produced from hiPSC, frozen and ready to use, perfectly characterized and of a size that allows the treatment of a pig that has undergone exposure to whole body irradiation developing a reversible hematological syndrome of category H3 according to the MEdical TREatment ProtocOLs for Radiation Accident Victims (METROPOL) classification. We will demonstrate that human hematopoietic graft from hiPSCs is involved in hematopoietic reconstitution.
Our strengths are our expertise in hematopoietic reconstitution, in the implementation of clinical trials (PHRC PRISME, NCT02814864), in the treatment of radiation victims and in the complementarity of a consortium with which we have been working for more than a decade. It is composed of academic researchers specializing in hematopoiesis, clinical hematologists, EFS Atlantic Bio GMP specializing in the production of advanced therapy medicinal products (ATMP) from from pluripotent stem cells and an SME; Phenocell, specialized in the production of clinical grade hiPSC banks.
The RESCUE project is a demonstration that it will be possible in the future to treat victims of an ARS with freezable, ready-to-use products after nuclear exposure or malevolent acts. This will radically increase the capacity to manage and treat high-dose irradiated patients. The civil and military repercussions are immense. The shortage of organs and the rapid development of tissue bioengineering mean that regenerative medicine will have to use these techniques, particularly for the treatment of radiation sequelae.
Monsieur Alain CHAPEL (Pôle Santé Environnement - Direction Santé)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
EFS Etablissement français du sang
CDR SA CENTRE DE RECHERCHE SAINT-ANTOINE
LBD Laboratoire de Biologie du développement
Phenocell PHENOCELL SAS
PSE-SANTE Pôle Santé Environnement - Direction Santé
Help of the ANR 498,977 euros
Beginning and duration of the scientific project: January 2020 - 36 Months