Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms

被引：27

作者：

Song, Yunejin ^{[1
,2
,3
]}

Lim, Jung-Yeon ^{[1
,2
,4
]}

Lim, Taekyu ^{[5
]}

Im, Keon-Il ^{[1
,2
]}

Kim, Nayoun ^{[1
,2
]}

Nam, Young-Sun ^{[1
,2
]}

Jeon, Young-Woo ^{[1
,2
,6
]}

Shin, Jong Chul ^{[7
]}

Ko, Hyun Sun ^{[8
]}

Park, In Yang ^{[8
]}

Cho, Seok-Goo ^{[1
,2
,6
,9
]}

机构：

[1] Catholic Univ Korea, Coll Med, Inst Translat Res & Mol Imaging, Seoul 06591, South Korea

[2] Catholic Univ Korea, Coll Med, Lab Immune Regulat, Convergent Res Consortium Immunol Dis, Seoul 06591, South Korea

[3] Catholic Univ Korea, Coll Med, Dept Biomed & Hlth Sci, Seoul 06591, South Korea

[4] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA

[5] Vet Hlth Serv Med Ctr, Dept Internal Med, Div Hematol Oncol, Seoul 05368, South Korea

[6] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Dept Hematol,Catholic Blood & Marrow Transplantat, Seoul 06591, South Korea

[7] CHA Univ, CHA Bundang Med Ctr, Dept Obstet & Gynecol, Seongnam 13496, South Korea

[8] Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, Seoul 06591, South Korea

[9] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Hematol, Banpodaero 222, Seoul 06591, South Korea

来源：

WORLD JOURNAL OF STEM CELLS | 2020年 / 12卷 / 09期

关键词：

Mesenchymal stem cells; Graft-versus-host disease; Umbilical cord; Cell therapy; Xenogeneic mouse model; Immunomodulation; SUPPRESS T-LYMPHOCYTE; VERSUS-HOST-DISEASE; STROMAL CELLS; INTERFERON-GAMMA; GROWTH-FACTOR; PROLIFERATION; ANTIGEN; BLOOD; TRANSPLANTATION; INTERLEUKIN-6;

D O I：

10.4252/wjsc.v12.i9.1032

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

BACKGROUND Mesenchymal stem cells (MSCs) are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties. Although human bone marrow-derived MSCs (BM-MSCs) were the most widely used MSCs in cell therapy until recently, MSCs derived from human umbilical cords (UC-MSCs) have gained popularity as cell therapy material for their ethical and noninvasive collection. AIM To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs. METHODS To analyze soluble factors expressed by MSCs, such as indolamine 2,3-dioxygenase, cyclooxygenase-2, prostaglandin E2 and interleukin (IL)-6, inflammatory environmentsin vitrowere reconstituted with combinations of interferon-gamma (IFN-gamma), tumor necrosis factor alpha and IL-1 beta or with IFN-gamma alone. Activated T cells were cocultured with MSCs treated with indomethacin and/or anti-IL-10. To assess the ability of MSCs to inhibit T helper 17 cells and induce regulatory T cells, induced T helper 17 cells were cocultured with MSCs treated with indomethacin or anti-IL-10. Xenogeneic graft-versus-host disease was induced in NOG mice (NOD/Shi-scid/IL-2R gamma(null)) and UC-MSCs or BM-MSCs were treated as cell therapies. RESULTS Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation abilities. BM-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-gamma, tumor necrosis factor alpha-alpha and IL-1 beta or IFN-gamma alone. UC-MSCs expressed more prostaglandin E2, IL-6, programmed death-ligand 1 and 2 in thein vitroinflammatory environment. Cyclooxygenase-2 and IL-10 were key factors in the immunomodulatory mechanisms of both MSCs. In addition, UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than BM-MSCs. UC-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host disease. CONCLUSION UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms involved. These findings suggest that UC-MSCs have distinct immunoregulatory functions and may substitute BM-MBSCs in the field of cell therapy.

引用

页码：1032 / 1049

页数：18

共 41 条

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