Cell Therapy and Graft Engineering for Chronic Graft-versus-host Disease.

Chronic graft-versus-host disease (cGVHD) is one of the most serious long-term complications of allogeneic haematopoietic stem cell transplantation (allo-HSCT), substantially impairing quality of life and increasing non-relapse mortality. This narrative review summarises current evidence on cellular therapies for cGVHD, focusing on mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs), with emphasis on graft source differences, GVHD prevention and immune reconstitution, cell source, manufacturing, dosing, concomitant immunosuppression, and endpoint definition, alongside emerging approaches such as NK/iNKT-cell strategies and engineered Tregs. Bone marrow transplantation is used as the primary reference platform, with peripheral blood stem cell transplantation and non-bone marrow-derived cell products included as contextual evidence where appropriate. Overall, Treg- and MSC-based therapies show promise for prevention and treatment; MSCs have the broadest clinical experience, whereas Treg-based approaches offer a more specific tolerance-restoring rationale. A key limitation is the inability to fully address tissue fibrosis. Treatment responses remain variable, durability is limited, and safety profiles require further optimisation. Clinical efficacy remains inconsistent, with a gap between mechanistic promise and clinically interpretable evidence. Future progress will depend on clearer clinical positioning, standardised cell products, prospective evaluation of steroid-sparing outcomes, GVHD-free or failure-free survival, patient-reported outcomes, and biomarker-guided immune monitoring. Thus, we propose practical recommendations for stratification and endpoint standardisation to enhance the clinical utility of cell therapy in chronic graft-versus-host disease.