Donor-Recipient Chimeric Cells (DRCC) Transplantation as the Bridging Therapy for Mitigating Total Body Irradiation-Induced Injury.

Abstract

In recent years, cell-based therapies have emerged as a promising approach for mitigating radiation-induced injury. Acute radiation syndrome (ARS) results from exposure to high doses of radiation over a short time period. This study aimed to compare the efficacy of donor-recipient chimeric cell (DRCC) therapy in mitigating ARS induced by a total body irradiation (TBI) dose of 10 gray (Gy). Thirty irradiated Lewis rats were employed as ARS models to assess the efficacy of systemic-intraosseous transplantation of different cellular therapies in five experimental groups (n=6/group): saline control, isogeneic bone marrow transplantation (isoBMT), allogeneic BMT (alloBMT), DRCC, and alloBMT+DRCC. DRCC were created by polyethylene glycol-mediated fusion of bone marrow cells from 24 ACI (RT1a) and 24 Lewis (RT11) rat donors. The creation of DRCC and chimeric state were confirmed by flow cytometry (FC) and confocal microscopy (CM). Recovery of blood parameters was evaluated via complete blood count analysis. GvHD (graft-versus-host disease) signs were assessed clinically and histopathologically using kidney, skin, and small intestine biopsies. FC and CM confirmed the fusion feasibility and the chimeric state of DRCC. A 100% mortality rate was observed in the saline control group, whereas a 100% survival was recorded following DRCC transplantation, correlating with significant recovery of peripheral blood parameters. Additionally, no clinical or histopathological signs of GvHD were observed after DRCC and alloBMT+DRCC transplantation. These findings confirm efficacy of DRCC in mitigating GvHD, promoting hematopoietic recovery, and increasing animal survival following TBI-induced ARS.​​ Moreover, tolerogenic and immunomodulatory properties of DRCC therapy support its feasibility for clinical applications. Therefore, this study introduces DRCC as an innovative bridging therapy for alleviating the acute effects of TBI, with broad implications for stem cell research and regenerative medicine.