Recherche biomédicale avancée et innovation

Cell therapy since the allograft to universal transplant. How to transform a concept in a clinical trial : application in the treatment of the side effects of radiotherapy

Alain Chapel

Cell therapy was demonstrated of main importance in the management of normal tissue radiation damage. Preclinical and clinical trial data suggest that mesenchymal stem cells (MSCs) are a practical and safe source of cells for stem cell-based therapies of severe tissue damage consecutive to radiation overexposure. MSCs were shown to migrate to damaged tissues supporting wound healing through a “cell drug” mode of action restoring skin and gut functions after irradiation. However, technical limits associated with large-scale ex vivo expansion indicate that alternative source is required to obtain sufficient cell numbers of the appropriate lineage to treat patients with severe disease.Based on this pluripotency and unlimited expansion potential, induced pluripotent stem cells (iPSCs) are considered a promising resource for regenerative medicine. Like naturally occurring stem cells, these artificially induced cells can self-renew and develop into almost any cell in the body (pluripotency). Clinical iPSC banks of selected universal donors should allow their use for large scale allogeneic grafts. Our consortium describes a GMP-grade system to produce hiPSCs, a cell population capable of reconstituting human hematopoiesis. We demonstrate that i) hiPSC-derived hematopoietic stem cells (HSCs) from healthy donor are capable of reconstituting a functional human hematopoiesis in a radio-induced aplasia preclinical model, ii) hiPSC-derived HSCs from aplastic anemia patients or acute leukemia affected patients retain this ability.Our study prepares a new approach of autologous graft (from the cells of the patient) of cells for healthy tissue damage after radiation exposure. It could potentially pave the way to the constitution of universal banks of stem cells, which would radically increase the capacity of support and treatment of tissue exposed to high doses of ionizing radiation and in the management of chronic late radiotherapy side effects.