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

TY - JOUR

T1 - Immunological properties of extraembryonic human mesenchymal stromal cells derived from gestational tissue

AU - Stubbendorff, Mandy

AU - Deuse, Tobias

AU - Hua, Xiaoqin

AU - Phan, Thang T

AU - Bieback, Karen

AU - Atkinson, Kerry

AU - Eiermann, Thomas H

AU - Velden, Joachim

AU - Schröder, Christine

AU - Reichenspurner, Hermann

AU - Robbins, Robert C

AU - Volk, Hans-Dieter

AU - Schrepfer, Sonja

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Differentiation

KW - Cell Movement

KW - Cell Proliferation

KW - Cells, Cultured

KW - Female

KW - Fetal Blood

KW - HLA-G Antigens

KW - Histocompatibility Antigens Class I

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Indoleamine-Pyrrole 2,3,-Dioxygenase

KW - Interferon-gamma

KW - Lymphocyte Culture Test, Mixed

KW - Male

KW - Mesenchymal Stem Cell Transplantation

KW - Mesenchymal Stromal Cells

KW - Mice

KW - Mice, Inbred BALB C

KW - Placenta

KW - Pregnancy

KW - T-Lymphocytes, Helper-Inducer

KW - Transforming Growth Factor beta1

KW - Transplantation, Heterologous

KW - Umbilical Cord

KW - Up-Regulation

U2 - 10.1089/scd.2013.0043

DO - 10.1089/scd.2013.0043

M3 - SCORING: Journal article

C2 - 23711207

VL - 22

SP - 2619

EP - 2629

JO - STEM CELLS DEV

JF - STEM CELLS DEV

SN - 1547-3287

IS - 19

ER -