Phenotypical and Functional Characterization of Bone Marrow Mesenchymal Stem Cells in Patients with Chronic Graft-versus-Host Disease

• Mesenchymal stem cells from patients after allogeneic hematopoietic stem cell transplantation are of host origin.
• Mesenchymal stem cells frequency is reduced in bone marrow of patients after allogeneic hematopoietic stem cell transplantation.
• Mesenchymal stem cells from patients with chronic graft-versus-host disease have normal proliferation and differentiation potential.
• Mesenchymal stem cells from patients with chronic graft-versus-host disease could effectively inhibit peripheral blood mononuclear cell proliferation.
• No increased senescence and apoptosis were observed in mesenchymal stem cells from patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is a critical complication after allogeneic hematopoietic stem cell transplantation. The conditioning therapy has been involved in the impairment of bone marrow (BM) mesenchymal stem/stromal cells (MSCs). However, the potential implication of MSCs in the pathophysiology of cGVHD has not been investigated. We analyzed expanded MSCs from patients with cGVHD and compared them with those from transplantation patients without cGVHD. The MSCs from both groups were of host origin and their reserves were comparable. They showed similar morphology, immunophenotype, population doubling times, self-renewal capacity, differentiation, and migration potential. The immunomodulatory potential of the 2 groups was also identical, they were both capable of inhibiting phytohemagglutinin-activated peripheral blood mononuclear cells (PBMCs) proliferation and inducing regulatory T cells after coculturing with CD4+ T cells, and the immunosuppressive factors were secreted similarly in both MSCs whether in normal culture or coculture with PBMCs. No significant differences were observed in the cellular senescence and apoptosis between 2 groups. In addition, MSCs from patients with cGVHD displayed normal phenotype and function compared with their counterparts from healthy donors, although reduced frequency in BM mononuclear cell fraction was observed in these patients. Taken together, our results suggest that MSCs do not seem to contribute to the pathogenesis of cGVHD and indicate the feasibility of autologous cell therapy in patients who are not completely responding to standard immunosuppressive therapy for cGVHD.