title: Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue.
abstract: 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 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 TH1 and TH2 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-γ stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-γ stimulation. Despite their lower IDO, HLA-G, and TGF-β1 expression, only CL-MSCs were able to reduce the release of IFN-γ by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cell-based 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-β play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.
authors.affiliation: 1 Transplant and Stem Cell Immunobiology Lab, University Heart Center Hamburg , Hamburg, Germany .
authors.forename: Mandy
authors.initials: M
authors.lastname: Stubbendorff
authors.forename: Tobias
authors.initials: T
authors.lastname: Deuse
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Hua
authors.forename: Thang T
authors.initials: TT
authors.lastname: Phan
authors.forename: Karen
authors.initials: K
authors.lastname: Bieback
authors.forename: Kerry
authors.initials: K
authors.lastname: Atkinson
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Eiermann
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.forename: Christine
authors.initials: C
authors.lastname: Schröder
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Sonja
authors.initials: S
authors.lastname: Schrepfer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D059951:HLA-G Antigens / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D014470:Umbilical Cord / Q000166:cytology*; D015854:Up-Regulation; D000097625:HLA-E Antigens
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D053773:Transforming Growth Factor beta1; D000097625:HLA-E Antigens