MSCs are capable of inducing Treg-like cells

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.

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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);  

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