The outcomes of several of these trials hint towards a beneficial immunomodulatory effect of MSC, but they are not conclusive 7. Multiple clinical trials with MSC in inflammatory disease and transplantation have been conducted, such as in graft versus host disease 4, kidney transplantation 5, and Crohn’s disease 6. Mesenchymal stromal cells (MSC) are studied as an experimental therapy for immunological disorders due to their diverse immunomodulatory properties 1, 2, 3. These data demonstrate that MP have immunomodulatory properties and have potential as a novel cell-free therapy for treatment of immunological disorders.
MPγ increased mRNA expression of PD-L1 in monocytes. MP and MPγ increased the percentage of CD90 positive monocytes, and MPγ but not MP increased the percentage of anti-inflammatory PD-L1 monocytes. However, MP and MPγ selectively bound to monocytes and decreased the frequency of pro-inflammatory CD14 +CD16 + monocytes by induction of selective apoptosis. MP and MPγ did not physically interact with T cells and had no effect on CD4 + and CD8 + T cells proliferation. MP exhibited ATPase, nucleotidase and esterase activity, indicating they are enzymatically active. Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape.
To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Hypothetically, living cells are a risk for tumor formation. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Mesenchymal stromal cells (MSC) are a promising therapy for immunological disorders.
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