Non-classical type I HLAs and B7 costimulators revisited: analysis of expression and immunomodulatory role in undifferentiated and differentiated MSC isolated from human umbilical cord Wharton's jelly

Abstract

Introduction. Wharton’s jelly (WJ), the main constituent of umbilical cord, emerged as a reliable and uncontroversial source of mesenchymal stem cells (MSC). WJ-MSC show unique ability in crossing lineage borders, therefore being capable to trans-ifferentiate towards mature cytotypes derived from the three germ layers. As other fetal-associated cells, WJ-MSC express several immunomodulatory molecules, essential during the initial phases of human development and for the processes linked to the tolerance of the mother to the semiallogeneic embryo. Very few data are present in literature on the maintenance of the immune privilege of the naïve cells after performing differentiation. Our previous work highlighted the expression of non-classical HLA molecules as HLA-G in WJ-MSC, together with a favorable combination of B7-1 and B7-2 costimulators. Methods. The aim of this work was extending the knowledge on the expression of immunomodulatory molecules by naïve and differentiated WJ-MSC. WJ-MSC underwent differentiation to osteoblasts, adipocytes and hepatocyte-like cells. Differentiated cells were analyzed, by RT-PCR, ICC and histological stains for the acquisition of the desired phenotypical features. We investigated also the differential expression of immune-related molecules in undifferentiated and differentiated cells. Moreover, we exploited the in vitro ability of such cells to suppress allogeneic lymphocyte proliferation in MLR experiments. Results. WJ-MSC expressed diverse immunomodulatory molecules which span from non-classical type I HLAs (i.e. HLA-E, -F, -G) , to further members of the B7 family, and of the CEA superfamily, for all of which in vivo immunomodulating functions are known. For some of these factors, we demonstrated for the first time their expression in WJ-MSC. In addition, we demonstrated for the first time that the expression of these molecules is maintained after performing osteogenic, adipogenic or hepatogenic differentiation. Conclusions. Present data should disclose new promising features for the in vivo application of WJ-MSC in allogeneic cell therapy settings.