Mesenchymal stromal cells (MSC) prelicensed with pro-inflammatory cytokines for improved survival and immunosuppressive properties following cryopreservation.
- Preserves the immunosuppressive function of MSCs following thawing.
- Improves effectiveness of transplanted MSCs following cryopreservation.
Mesenchymal stromal cells are adult multipotent stem cells derived from bone marrow and other tissues. MSCs are used in clinical settings for anti-inflammatory and regenerative medicine applications. In most instances, the MSCs are cryobanked prior to use and thawed prior to use in the clinic. Before MSCs are administered, they are exposed to pro-inflammatory cytokines in a process called "licensing." In the clinic, the use of MSCs has met with mixed results and many large trials have failed to meet their endpoints or show consistent efficacy. It has been shown that cryopreservation increases MSC susceptibility to T-cell mediated apoptosis, increasing the variability of the cells after thaw and transplantation.
Emory University researchers have demonstrated the large differences between the immunosuppressive function of fresh MSCs and cryopreserved MSCs. In order to prevent this freeze/thaw-induced loss of MSC immunosuppressive function, the team has tested the effect of interferon gamma (IFNγ) prelicensing, in which MSCs are treated with IFNγ prior to licensing and cryopreservation. Prelicensing inhibits CD8 T-cell degranulation and prevents the death of MSCs upon peripheral blood mononuclear cell (PBMC) co-culture. Additionally, prelicensing results in the upregulation of the immunosuppressive enzyme IDO. This opportunity may improve or enable many MSC products and cellular therapies.
Publications: Chinnadurai, R. et al. (2016). Stem Cells, 34(9), 2429-42.