We evaluated the immunomodulatory properties of MSC-NTF cells and their effects on T and B regulatory cells.

MSC-NTF cells (NurOwn®) are autologous, differentiated bone-marrow derived mesenchymal stem cells (MSC) that secrete neurotrophic factors (NTFs), regulatory miRNAs that demonstrate neuroprotection and immunomodulation in preclinical models and are currently under evaluation in phase 2 progressive MS and phase 3 ALS trials.  Disordered T and B regulatory cell function has been implicated in the pathogenesis of ALS and MS.  Furthermore, IL-10 production by regulatory B cells, may ‘regulate the regulators’, and has been viewed as a protective mechanism in ALS and MS animal models, possibly through effects on microglial networks.  

MSC-NTF cells were generated from healthy controls and were co-cultured with human peripheral blood mononuclear Cells (PBMC) or isolated B cells. The effect of MSC-NTF cells on proliferation of T or B cells and on induction of regulatory T or B cells was evaluated using flow cytometry. ELISA was used to measure secretion of different cytokines and IgM.

MSC-NTF cells inhibited IFN-g and TNF-a secretion and CD4+/ CD8+ T cell proliferation when co-cultured with activated PBMCs, and induced CD4+CD25+FoxP3+ regulatory T cells.  MSC-NTF cells did not affect B cells proliferation, however we observed that they induced CD24^hiCD38^hi regulatory B cells, stimulated IL-10 secretion, and inhibited B cell IgM secretion.

Neuroinflammation is a prominent pathological feature of ALS and progressive MS.  Reduced T and B regulatory function may contribute to disease progression, and lower IL-10 levels may be associated with reduced ALS function and with higher disability and MRI lesion load in secondary progressive MS. The immunomodulatory properties of MSC-NTF cells, including their effects on T and B regulatory cells, combined with neuroprotective and repair mechanisms may extend the potential therapeutic benefits of MSC-NTF cells.