HLA-G and CD152 Expression Levels Encourage the Use of Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells as an Alternative for Immunosuppressive Therapy

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 8; p. 1339
• Main Authors: Zoehler, Bernardo, Fracaro, Letícia, Boldrini-Leite, Lidiane Maria, da Silva, José Samuel, Travers, Paul J, Brofman, Paulo Roberto Slud, Bicalho, Maria da Graça, Senegaglia, Alexandra Cristina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.04.2022; MDPI
• Subjects: Adipose tissue; Alleles; Antibodies; Antigens; Autoimmune diseases; Body fat; Bone marrow; CD40 antigen; CD80 antigen; CD86 antigen; Cell Proliferation; Cells, Cultured; CTLA-4 protein; Cytokines; Cytotoxicity; Dental pulp; dental pulp tissue; Exons; Graft versus host disease; Growth factors; Histocompatibility antigen HLA; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; HLA-G molecule; Hypoxia; Immune system; Immunosuppression; Immunosuppression Therapy; Immunosuppressive agents; immunosuppressive therapy; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Lymphocytes; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; mesenchymal stromal cell; Mesenchyme; Next-generation sequencing; Peripheral blood mononuclear cells; Stromal cells; Umbilical cord; Umbilical Cord - metabolism; umbilical cord tissue; γ-Interferon; New York; United States > US; immunosuppressive therapy; HLA-G molecule; umbilical cord tissue; costimulatory molecules; adipose tissue; dental pulp tissue; mesenchymal stromal cell; immunosuppressive molecules
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11081339

Mesenchymal stromal cells (MSCs) have been used in immunosuppressive therapy due to their therapeutic effects, with the HLA-G molecule seeming to play a fundamental role. This work evaluated alternative MSC sources to bone marrow (BM), namely, umbilical cord tissue (UC), adipose tissue (AD) and dental pulp tissue (DP), and the influence of interferon-γ (IFN-γ) and hypoxia on the cultivation of these cells for use in immunosuppression therapies. Expression of costimulatory markers CD40, CD80 and CD86 and immunosuppressive molecules CD152 and HLA-G was analyzed. Lymphocyte inhibition assays were also performed. Sequencing of the HLA-G gene from exons 1 to 5 was performed using next-generation sequencing to determine the presence of alleles. UC-derived MSCs (UCMSCs) expressed higher CD152 and HLA-G1 under standard cultivation. UCMSCs and DP-derived MSCs (DPSCs) secreted similar levels of HLA-G5. All MSC sources inhibited the proliferation of peripheral blood mononuclear cells (PBMCs); growth under regular versus hypoxic conditions resulted in similar levels of inhibition. When IFN-γ was added, PBMC growth was inhibited to a lesser extent by UCMSCs. The HLA-G*01:04:01:01 allele appears to generate a more efficient MSC response in inhibiting lymphocyte proliferation. However, the strength of this conclusion was limited by the small sample size. UCMSCs are an excellent alternative to BM in immunosuppressive therapy: they express high concentrations of inhibitory molecules and can be cultivated without stimuli, which minimizes cost.