Immunomodulation by placenta-derived decidua stromal cells. Role of histocompatibility, accessory cells and freeze-thawing

Background aims: Human placenta-derived decidua stromal cells (DSCs) are newly introduced stromal cells that have successfully been used in several clinical trials for the treatment of acute inflammatory diseases. Despite pub-lished data about DSCs, deeper exploration of mechanisms of action and crosstalk with other immune cells need to be explored. Methods: In mixed lymphocyte culture (MLC), the splenocytes from Balb/c or B6 mice were stimulated using mitogen (concanavalin A), allogeneic (B6 or Balb/c splenocytes) or xenogeneic activation with human periph-eral blood mononuclear cells. Results: When 10% of the mouse bone marrow-derived-MSC, being autologous, allogeneic or haploidentical (from F1), was added, >95% inhibition was seen. Using human (h)-DSCs, the inhibitory capacity was a median 68% as a xenogeneic immunomodulatory cell when used in mitogen and allogeneic setting in mice MLC. How-ever, when human peripheral blood mononuclear cells were used as stimulator for mouse splenocyte (xenoge-neic MLC), hDSC showed a median inhibition of 88%. We explored the presence and function of monocytes in the immunomodulatory function of stromal cells. CD14+ monocyte cells reduced the immunosuppressive effect by hDSC. hDSCs did not show any inhibitory effect on natural killer cell activation and proliferation by interleukin-2. In contrast DSCs increased natural killer proliferation by a median of 58%. Fresh or frozen-thawed hDSCs had similar inhibitory effects on human T-cell proliferation (both allo-stimulation and mitogen stimulation) in vitro. Cell viability at room temperature during 24 h was similar using fresh or freeze-thawed DSCs. Conclusions: To conclude, histocompatibility and CD14+ monocyte cells had an impact on hDSC immunomo-dulation but frozen-thawed or freshly prepared cells did not. (c) 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)