Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue

Stem Cells Dev. 2013 Oct 1;22(19):2619-29. doi: 10.1089/scd.2013.0043. Epub 2013 Jun 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Fetal Blood / cytology*
  • HLA-G Antigens / biosynthesis
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class II / biosynthesis
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis
  • Interferon-gamma / metabolism
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Placenta / cytology*
  • Pregnancy
  • T-Lymphocytes, Helper-Inducer / immunology
  • Transforming Growth Factor beta1 / biosynthesis
  • Transplantation, Heterologous
  • Umbilical Cord / cytology*
  • Up-Regulation

Substances

  • HLA-E antigen
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Transforming Growth Factor beta1
  • Interferon-gamma