Application de la thérapie cellulaire autologue dans le contexte des irradiations accidentelles hétérogènes.

J. M. Bertho, European radiation research 2004, the annual congress of the european society for radiation biology, 25-28/08/2004, Budapest, Hongrie.

  Although rare, accidentally irradiated victims remain difficult to treat, mainly due to the complexity of radiation-induced physiopathology. In fact, the acute radiation syndrome (ARS) appears as the addition of several pathologies such as the hematopopietic syndrome, the gastro-intestinal syndrome and the cerebro-vascular syndrome, but also kidney and lung disease or cutaneous syndrome. As a result, the overall long term survival of victims irradiated at whole body doses above 5 Gy is about 16%, highlighting the need for new therapeutic approaches of accidentally irradiated victims.

Over the past decade, increasing amount of data indicated that ex vivo expanded hematopoietic cells are highly efficient in the treatment of chemotherapy-induced aplasia. Thus, it was proposed that autologous hematopoietic cell therapy could be applied to the treatment of accidental radiation-induced hematopoietic syndrome. Such an approach is based upon two hypothesis. The first hypothesis is the heterogeneous nature of accidental irradiation, which suggests the existence of bone marrow sites that are protected from irradiation, as it was demonstrated in several radiation accidents. The second hypothesis is the possibility to expand hematopoietic stem cells that were previously irradiated. This was also demonstrated by several teams, although with a limited efficiency. As compared to classical stem cell transplantation used in recent radiation accidents, such a cell therapy approach might have several advantages, among which the autologous context of cell therapy, which avoid risks of GVHD, graft rejection, and conditioning regimen. However, such a protocol needs important developments, including the technical requirements for hematopoietic cell expansion. Moreover, these studies need to be developed in a large animal model such as non-human primates with an heterogeneous irradiation that might be representative of an accidental irradiation situation. Such a model may help to define the limits of cell therapy, both for dose range and therapeutic efficiency.  Despite these limitations, autologous cell therapy appears as a promising approach, that may be applied with other cell types such as mesenchymal stem cells or multipotent adult stem cells. Such protocol may be useful also for the study of physiopathology of the ARS.