The immunomodulatory activity of human umbilical cord blood‐derived mesenchymal stem cells in vitro

Abstract

SummaryBone marrow-derived mesenchymal stem cells (BM-MSC) are currently being investigated in preclinical and clinical settings because of their selfrenewal and multipotent differentiative capacity or their immunosuppressive function. However, BM may be detrimental because of the highly invasive donation procedure and BM-MSC decline with age. Therefore, MSC derived from other sources have been considered as an alternative. However, there is only limited knowledge on their immunomodulatory properties. Human umbilical cord blood (UCB) cells are good substitutes for BM-MSC because of the immaturity of newborn cells. In this study, we successfully isolated MSC from UCB. The morphological phenotypes, cell cycle status, surface markers and differentiation potential of these clonally expanded cells are consistent with BM-MSC. Furthermore, UCB-MSC expanded in vitro retain low immunogenicity and an immunomodulatory effect. Flow cytometry analysis showed that UCB-MSC did not express CD40, CD40 ligand, CD80, CD86 and major histocompatibility complex class II molecules. We have demonstrated that UCB-MSC are incapable of inducing allogeneic peripheral blood mononuclear cell (PBMC) proliferation and have a dose-dependent inhibition of PBMC immune responses in mixed lymphocyte reactions (MLR) and phytohaemagglutinin activation assays, even after interferon-c treatment. Additionally, we have found that UCB-MSC can suppress the function of mature dendritic cells. Using transwell systems, we have demonstrated an inhibition mechanism that depends on both cell contact and soluble factors. Based on the findings we conclude that banked UCB could serve as a potential alternative source of MSC for allogeneic application in the future.

Perivascular Ancestors of Adult Multipotent Stem Cells

“…The morphology, division characteristics, and surface markers of CBMSCs are similar to those of bone marrow-derived MSCs, 59,60 except for some differences in the expression of CD105 and CD44. 61 More important, CBMSCs have also been identified as perivascular cells expressing CD146, platelet-derived growth factor ␤, alkaline phosphatase, and NG2, but not CD34 or CD45.…”

Mitochondrial Function and Energy Metabolism in Umbilical Cord Blood- and Bone Marrow-Derived Mesenchymal Stem Cells

“…hMSCs are traditionally derived from adult tissues, such as adipose and bone marrow, but cells from these sources seem to lose their potential during aging; and, therefore, alternative sources are sought from postnatal tissues, such as umbilical cord blood [1,[5][6][7][8][9]. Umbilical cord blood-derived MSCs (UCBMSC) are now considered a potential substitute for bone marrow-derived mesenchymal stem cell (BMMSC) to overcome the aging problem, as they are derived from an in vivo microenvironment more similar to bone marrow with characteristic properties for hMSCs [5,[10][11][12][13][14][15].…”

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

“…Immunosuppressive treatments that increase graft survival are undesirable, since it has been shown that a correlation exists between the length of exposure to immunosuppressive drugs and the risk of malignancy after stem cell transplantation. Recent results have shown that mesenchymal stem cells from umbilical cord blood, dental pulp, PDL and bone marrow have immunosuppressive properties in vitro [43][44][45]. Moreover, the clonogenic nature of adult stem cells represents an advantage heterogeneous stem cell populations resulting in a more reproducible, potent immunosuppressive effect in patients [46].…”