UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELLS AS AN ALTERNATIVE TO BONE MARROW IN IMMUNOSUPPRESSIVE THERAPY

Background Due to their immunomodulatory characteristics, mesenchymal stromal cells (MSC) have become an option in immunosuppressive therapy. HLA-G expression appears to play a key role in immunomodulation, inhibiting proliferation of immune cells and inducing activation of regulatory cells, modulating host‘s immune response. Thus, identifying a source of MSC with high HLA-G expression can be a good strategy for future treatments. Methods MSC from umbilical cord tissue (UCT) (n=3) were compared to a sample of bone marrow (BM) (n=1) under the following growing conditions: (i) standard cultivation; (ii) stimulation of interferon-γ (IFN-γ); and (iii) hypoxia condition (2% O2). Expression of CD14, CD73, CD34, CD19, CD166, CD29, CD45, CD90, HLA-DR and CD105 markers and co-stimulatory CD40, CD80 and CD86 markers were analyzed. The analysis of CD152 molecule (intracellular isoform) and membrane HLA-G1 isoform was performed by flow cytometry to study the expression of immunosuppressive molecules. The analysis of soluble HLA-G5 isoform was performed by enzyme-linked immunosorbent assay (ELISA). For analysis of the immunosuppressive potential of MSCs, a lymphocyte (PBMCs) inhibition assay was performed in proportions 1:2 and 1:10 (MSC:PBMC). Results The expression of cellular markers was following that required by the International Society for Cell and Gene Therapy. All samples showed negative expression for co-stimulatory markers CD40, CD80 and CD86 and positive expression for CD152. CD152 and HLA-G1 molecules were more expressed by UC when grown under normal conditions (p=0.0018 and p=0.0003, respectively) or hypoxia (p=0.0057 and p Conclusion We observed that IFN-γ was able to trigger an increase in inhibitory capacity of BM MSC, but not in UCT-MSC, being indicated in cultivation of BM MSC used for immunosuppressive therapy. In addition, UCT-MSC proved to be an efficient alternative to BM MSC. UCT-MSC showed an advantage in the expression of immunosuppressive