Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells for regenerative therapies

Aims: Mesenchymal stem cells (MSCs) are of particular interest for their potential application in cell therapies. In this study, we investigate the immunogenicity of human umbilical cord-derived MSCs (clMSCs) and their immunogenic differences to adult bone marrow-derived MSCs (bmMSCs). Methods: clMSCs and bmMSCs were characterized for MSC markers, their multipotent capacity and their proliferation activity in vitro. Expression of immunogenic surface markers under normal (MHC-I, β2-microglobulin, MHCII, costimulatory molecules) was analyzed by flow cytometry. Cells were transduced for firefly luciferase expression and transplanted for in vivo bioluminescence imaging (BLI). In vivo immune response was evaluated 5 days after clMSC and bmMSC transplantation by ELISPOT for TH1 and TH2 response. Results: Due to their immature state, clMSCs had significantly lower HLA-I expression, higher production of tolerogenic TGF-β and IL-10 and significant higher proliferation activity (p=0.01). With bmMSCs a significantly stronger in vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation could be seen. IFNγ at 25ng/ml caused opposing effects on both MSC lines, up-regulating HLA-I and HLA-DR expression but also increasing intracellular HLA-G and surface HLA-E, augmenting TGF-β and IL-10 release. clMSCs showed decreased spot frequencies for IFNγ (42±40 vs. 322±78) and IL4 (59±61 vs. 220±103) in ELISPOT assays compared to bmMSCs (p=0.001 for IFNγ+IL4). BLI confirmed delayed rejection of clMSCs, resulting in increased cell survival (clMSC: 10.9±1.2 days vs. 7.2±0.9; p<0.01). Conclusions: Since clMSCs can be easily obtained at birth from the umbilical cord, these cells may provide a promising stem cell source for allogeneic transplantation.