Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues.
Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. In this study, we conducted a comparative analysis of the immunomodulatory properties of MSCs derived from adult human tissues including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ). Using a multiple cytokine detection assay, we showed that there were no significant differences in levels of secreted factors from non-stimulated MSCs. We compared the immunosuppressive effect of BM-MSCs, AT-MSCs, CB-MSCs, and WJ-MSCs on phytohemagglutinin-induced T-cell proliferation. AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed mitogen-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, the expression of hepatocyte growth factor, IL-10, transforming growth factor-beta(1), cyclooxygenase (COX)-1, and COX-2 were unchanged in MSCs treated with IFN-gamma and/or TNF-alpha, while indoleamine 2,3-dioxygenase (IDO) expression increased. IFN-gamma and/or TNF-alpha produced by activated T-cells were correlated with induction of IDO expression by MSCs, which, in turn, suppressed T-cell proliferation. These findings suggest that MSCs derived from AT, CB, or WJ could be substituted for BM-MSCs for treatment of allogeneic conflicts.
Yoo
Keon Hee
KH
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jang
In Keun
IK
Lee
Myoung Woo
MW
Kim
Hyo Eun
HE
Yang
Mal Sook
MS
Eom
Youngwoo
Y
Lee
Jong Eun
JE
Kim
Young Jin
YJ
Yang
Seong Kyu
SK
Jung
Hye Lim
HL
Sung
Ki Woong
KW
Kim
Cheol Woo
CW
Koo
Hong Hoe
HH
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D016207:Cytokines