The Research on irradiated healthy tissues regeneration Laboratory (LR2I) has been created from Radiopathology and Experimental Therapy Laboratory (LRTE) and is directed by Radia Tamarat. It aims to develop new therapeutic approaches, particularly cell therapy, to treat lesions induced by high doses of ionizing radiation.
Areas of research
New therapeutic hopes have recently appeared on the horizon, with the introduction of cell therapy into the treatment of necrotic lesions in human tissue induced by accidental irradiation or following radiotherapy. Following its initial clinical successes, the Institute is currently developing a research program (2009-2013) at the LRTE, in partnership with HIA Percy (plastic surgery department), the cell therapy unit of the Armed Forces Blood Transfusion Center (CTSA) and the hematology department at the Saint-Antoine teaching hospital. The program is structured around five areas:
- Production of adult stem cells with a therapeutic effect.
Different types of clinical-grade adult stem cell are produced by the CTSA’s cell therapy unit. The mesenchymal stem cells are the reference adult stem cells of our research program. The use of cryogenically preserved stem cells in particular is being tested with a view to setting up cell banks.
- Quantifying the contribution of cell therapy to two different experimental models at a preclinical stage.
Two localized irradiation models were chosen: on the skin and in the colorectal area. When applied to rodents and mini-pigs, they produce musculocutaneous ulceration and colorectal ulceration similar to the lesions observed in accident victims or radiotherapy patients. The treatment of animals using stem cells allows researchers to define the relevant clinical procedures for the use of stem cell grafts in both cases: number of cells, injection channels, injection frequency, comparison of the therapeutic effectiveness of different stem cells, possibility of creating cell banks, etc.
- To identify the modes of action of adult stem cells in the restoration of irradiated tissues.
The initial hypothesis is that adult stem cells have pro-angiogenic, immunomodulating, and neurogenic properties. The aim of the program is to explore the mechanisms of implantation, survival, and proliferation of stem cells in irradiated tissues with regard to these properties. Another aim is to identify the capability to differentiate between these cells and/or the possibility of selective secretion of pro-cicatrizing factors in response to the microenvironment associated with the irradiated tissues.
- To ensure the absence of side-effects to the use of adult stem cells.
The administration of adult stem cells to improve the healing of necrotic tissues after irradiation must be free of harmful side-effects, and most notably without any risk of canceration. The impact of MSC grafting on the formation of tumors is studied based on an experimental model of chemically-induced murine colic adenocarcinoma developed by the INSERM U673 team. The effect, if any, is characterized before and after a localized irradiation which sterilizes the cancerous cells.
- To obtain a medical consensus on the use of adult stem cells in the treatment of irradiated tissues.
Medical teams in charge of victims of accidental radiation are involved in the various stages of this program. Efforts will be made to obtain an international consensus concerning the use of cell therapy in the treatment of severe lesions in tissues irradiated at high doses.
Specialties and researchers
Alain Chapel (PhD)
Valérie Holler (PhD)
Christine Linard (PhD, HDR)
Noëlle Mathieu (PhD)
Alexandra Sémont (PhD)
Radia Tamarat (PhD)
Christelle Demarquay (technician)
Bruno Lhomme (technician)
Claire Squiban (technician)