Mesenchymal stromal cells (MSCs) are promising tools for the treatment of autoimmune and inflammatory diseases. These multipotent stromal cells possess innate immunomodulatory properties that can be significantly enhanced by co-culture with peripheral blood mononuclear cells (PBMCs).
Researchers at the Institute’s Center of Research in Myology and their colleagues studied the mechanisms underlying the conditioning of MSCs by PBMCs in vitro and their benefits in an animal model of myasthenia gravis.
MSCs extracted from human adipose tissue that were left at rest (MSCsr), conditioned by PBMCs (MSCsb) or activated by the pro-inflammatory molecule interferon (IFN)-γ (MSCsγ) were compared in terms of gene expression profiles, phenotypes and functional capacities.
The results show that:.
- conditioning with PBMCs triggers the expression of a specific panel of genes (244 genes involved, particularly in matrix remodelling and paracrine and autocrine communications),
- an increase in surface markers CD26, CD54 and CD273 and intracellular molecules IDO1 and PTGS2 is observed in CSMc.
These results highlight the dependence of transcriptomic and phenotypic signatures on treatment.
The authors also highlighted that:.
- proteins differentially modulated by PBMCs, CSMs or CSMcs can be classified into six categories,.
- conditioning generated phenotypic changes in certain PBMC populations,
- T-cell proliferation was inhibited by CSMcs,
- when injected into the NSG-MG mouse model, CSMc provided significant relief.
This integrative study establishes distinct conditioning signatures, suggests molecular mechanisms, and highlights the therapeutic potential of CSMc, providing a solid framework for advancing cell therapies in the field of autoimmune diseases.
