Exposure to high doses of ionizing radiation results in injury to multiple organs causing acute radiation syndrome. Bone marrow transplant (BMT) is an effective strategy to replace and regenerate injured stem cells, it has proven to be very successful in mitigating radiation induced acute injury to the bone marrow (BM- ARS). However at higher radiation doses and for non-hematopoietic injuries, BM mitigation alone is not sufficient to rescue from mortality. For instance, acute radiation injury to the gastro-intestinal tract (GI-ARS) is not mitigated by BMT or cytokine therapies. We have shown that GI-ARS can be successfully mitigated by bone marrow adherent stromal cell transplant (BMASCT), consisting mainly of stromal and myeloid cells. BMASCT in its current form is limiting when a large population is at risk, HLA libraries and well as allogeneic cell transplant therapies are essential to developing this therapy for a large population. Current application proposes various strategies to develop a radiomitigating cell product that can be used in a mass casualty scenario.
Radiation-induced gastrointestinal injury is a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. Radiation injury occurring within days after exposure is classified as ?acute injury? and often associated with direct damage to the stem cell and its niche, including the stroma and microvasculature. Late injury, which manifests months to years after exposure, is due to persistent oxidative and inflammatory signaling, aberrant stem cell regeneration, damage to the vascular stroma and scaring. Among various pharmacological approaches used, cell transplantation is one of the most effective strategies in treating radiation injury. The proposal delineate various strategies to optimize and enhance stromal cell therapy for the treatment of GI-ARS.
