The effect of bone marrow-derived mesenchymal stem cells to induce PD-L1 molecule on splenic lymphocytes

Mesenchymal stem cells are non-hematopoietic stromal cells that are used in the treatment of many chronic and autoimmune diseases by modulating the immune system. Due to the limitations of using autologous mesenchymal stem cells, the use of allogeneic stem cells is a promising therapeutic approach in the treatment of immunological disorders. This study aimed to investigate the ability of allogeneic mesenchymal stem cells to induce Programmed death-ligand 1(PD-L1) expression on the surface of splenic lymphocytes and the role of this molecule in the mesenchymal stem cell-treated cells tolerogenicity. 

This study was conducted from February 2019 to December 2020 in the department of Immunology of Mazandaran University of medical sciences. Mesenchymal stromal cells were isolated from the femur and tibia of C57 mice. C57 bone marrow-derived mesenchymal stem cells were co-cultured with allogeneic BALB/c splenic cells. After 72 hours, the expression of PD-L1 on the surface of splenic lymphocytes was evaluated by flow cytometry. Interferon-gamma (IFN-γ) and Interleukin-10 (IL-10) cytokine assay were done in the cell culture supernatant. Mesenchymal stem cell-treated BALB/c lymphocytes were then exposed to allogeneic C57 splenocyte as stimuli in the mixed lymphocyte reaction (MLR) and the rate of proliferation was assessed by CFSE.

The amount of PD-L1 positive BALB/c splenic lymphocytes were significantly increased after allogeneic C57 mesenchymal stem cells exposure (P=0.001). The levels of IFN-γ and IL-10 cytokines in the supernatant of cell culture also increased significantly (respectively, P=0.0009, P=0.01). C57 splenocytes proliferation notably decreased after mesenchymal stem cell-treated BALB/c lymphocytes exposure compared to the group were cultured with naïve BALB/c lymphocytes (P=0.002).

Allogeneic mesenchymal stem cells are capable to induce of PD-L1 on the surface of lymphocytes. PD-L1 expression on mesenchymal stem cell-treated cells makes them less immunogenic than naïve cells. These tolerogenic cells can reduce allogeneic responses. It seems that PD-L1 plays an important role in mesenchymal stem cell immunomodulation.