Lin Y, Gu Q, Lu S, et al. Ruxolitinib Improves Hematopoietic Regeneration by Restoring Mesenchymal Stromal Cell Function in Acute Graft-Versus-Host-Disease. Journal of Clinical Investigation. 2023; (doi: 10.1172/JCI162201).
Research finds the JAK1/2 inhibitor ruxolitinib mitigates hematopoietic dysfunction in the setting of acute graft-versus-host disease (aGVHD), which often develops after allogeneic hematopoietic stem cell transplantation. Using a mouse model of aGVHD, investigators conducted single-cell RNA sequencing of non-hematopoietic bone marrow (BM) cells. They found evidence of abnormal metabolism, reduced cell ratio, compromised differentiation potential, and impaired hematopoietic supportive function in BM mesenchymal stromal cells (BMSCs). Introduction of ruxolitinib blocked the JAK2/STAT1 pathway, thus restoring BMSC function and improving hematopoietic regeneration. Recipient BMSCs exhibited long-term improvement in aGVHD, characterized by better proliferation ability, mitochondrial metabolism capacity, crosstalk with donor-derived hematopoietic stem/progenitor cells, and adipogenesis/osteogenesis potential. Findings culled from the murine model were subsequently confirmed in human samples.
Tags: Graft versus host disease, Acute GVHD, aGVHD, grafts, ruxolitinib, graft, graft-versus-host disease, graft-vs-host disease, graft-versus-host