Immunological Properties of Extraembryonic Human Mesenchymal Stromal Cells Derived from Gestational Tissue

Mandy Stubbendorff, Tobias Deuse, Xiaoqin Hua, Thang T. Phan, Karen Bieback, Kerry Atkinson, Thomas H. Eiermann, Joachim Velden, Christine Schröder, Hermann Reichenspurner, Robert C. Robbins, Hans-Dieter Volk (+1 others)
2013 Stem Cells and Development  
Mesenchymal stromal cells (MSCs) have been isolated from many tissues, including gestational tissue. To date, a study comparing the properties and suitability of these cells in cell-based therapies is lacking. In this study, we compared the phenotype, proliferation rate, migration, immunogenicity, and immunomodulatory capabilities of human MSCs derived from umbilical cord lining (CL-MSCs), umbilical cord blood (CB-MSCs), placenta (P-MSCs), and Wharton's jelly (WJ-MSCs). Differences were noted
more » ... rences were noted in differentiation, proliferation, and migration, with CL-MSCs showing the highest proliferation and migration rates resulting in prolonged survival in immunodeficient mice. Moreover, CL-MSCs showed a prolongation in survival in xenogeneic BALB/c mice, which was attributed to their ability to dampen T H 1 and T H 2 responses. Weaker human cellular immune responses were detected against CL-MSCs and P-MSCs, which were correlated with their lower HLA I expression. Furthermore, HLA II was upregulated less substantially by CL-MSCs and CB-MSCs after IFN-g stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-g stimulation. Despite their lower IDO, HLA-G, and TGF-b1 expression, only CL-MSCs were able to reduce the release of IFN-g by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cellbased strategies, as they are hypo-immunogenic and show high proliferation and migration rates. In addition, these studies show for the first time that although immunomodulatory molecules HLA-G, HLA-E, and TGF-b play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.
doi:10.1089/scd.2013.0043 pmid:23711207 fatcat:2w4o2umgyfchfokh5ngdrgdvuy