Pre-HSCT conditioning and extracellular mitochondria impact on GVHD
Vijayan V, Yan H, Lohmeyer JK, et al. Extracellular Release of Mitochondria Induced by Pre-Hematopoietic Stem Cell Transplant Conditioning Exacerbates GVHD. Blood Advances. 2024; (doi: 10.1182/bloodadvances.2023012328).
A new approach for graft-versus-host disease (GVHD) prevention after hematopoietic stem cell transplantation (HSCT) centers around the tissue injury that occurs during pre-procedure cytotoxic conditioning. The conditioning process mediates the extracellular release of damaged mitochondria, which subsequently activate host antigen-presenting cells (APCs). The elevated levels of MHC-II, co-stimulatory CD86, and pro-inflammatory cytokines expressed by the stimulated host APCs promote increased activation of alloreactive donor T lymphocytes. In mice undergoing MHC-mismatched HSCT, introduction of purified syngeneic extracellular mitochondria resulted in host APC activation and increased GVHD. A novel intervention for preventing GVHD might entail reducing the extracellular release of impaired mitochondria following pre-HSCT conditioning, the authors write.