A new study has demonstrated that mesenchymal stromal cells can induce cells that resemble regulatory T-cells in vitro. The MSC-induced Treg-like cells have potential to constitute more effective cellular therapies for chronic inflammatory diseases.
Researchers at the Instituto de Medicina Molecular (Lisbon, Portugal) have demonstrated for the first time that mesenchymal stromal cells (MSCs) can induce cells that closely resemble regulatory T-cells (Tregs). The MSC-induced Treg-like cells have the potential to constitute more effective cellular therapies for the treatment of chronic inflammatory diseases. The pre-clinical study was recently published in Stem Cells, supporting future clinical trials.
Tregs play a critical role in immune tolerance; however, obtaining sufficient numbers of Tregs for therapies is very difficult. Rita Azevedo (Instituto de Medicina Molecular), who led this latest study, sought to determine whether MSC can induce and/or expand Tregs in vitro.
“Finding alternative sources of stable Treg induction might produce a large enough number for effective treatment uses” Azevedo explained. “But thus far, the potential of MSC to recruit Treg has been poorly understood.”
To investigate the mechanisms of MSC-mediated immunomodulation further, human peripheral blood mononuclear cells, collected from healthy donors, were co-cultured with allogeneic bone marrow-derived MSCs which were expanded in xenogeneic-free conditions. After 14 days, the results demonstrated that Treg counts and frequency were increased four- and six-fold respectively.
Moreover, the MSC-induced Treg-like cells resemble Treg functionally and their DNA methylation profile is like that of natural Treg, indicating that the population was stable. The results demonstrate that MSC-induced Treg-like cells have potential application as a cellular therapy in clinical settings where immune tolerance is compromised.
Azevedo concluded that “the co-administration of MSC and Treg might have the potential to constitute a more effective cellular therapy approach by harnessing the suppressive capacity of both these immunomodulatory populations.”
Sources: Azevedo R, Minskaia E, Fernandes-Platzgummer A et al. Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion of human conventional CD4 T cells in vitro. Stem Cells. doi:10.1002/stem.3185 (2020) (Epub ahead of print); https://stemcellsportal.com/press-releases/novel-method-produces-life-saving-t-cells-mesenchymal-stromal-cells