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, Sonja Schrepfer

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2619-2629
Number of pages11
JournalStem Cells and Development
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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