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

Yunejin Song; Jung-Yeon Lim; Taekyu Lim; Keon-Il Im; Nayoun Kim; Young-Sun Nam; Young-Woo Jeon; Jong Chul Shin; Hyun Sun Ko; In Yang Park; Seok-Goo Cho

doi:10.4252/wjsc.v12.i9.1032

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

World J Stem Cells. 2020 Sep 26;12(9):1032-1049. doi: 10.4252/wjsc.v12.i9.1032.

Authors

Affiliations

¹ Institute for Translational Research and Molecular Imaging, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
² Division of Hematology Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, South Korea.
³ Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam 13496, South Korea.
⁴ Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.

Abstract

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 environments in vitro were reconstituted with combinations of interferon-gamma (IFN-γ), tumor necrosis factor alpha and IL-1β or with IFN-γ 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-2Rγ^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-γ, tumor necrosis factor alpha-α and IL-1β or IFN-γ alone. UC-MSCs expressed more prostaglandin E2, IL-6, programmed death-ligand 1 and 2 in the in vitro inflammatory 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.

Keywords: Cell therapy; Graft-versus-host disease; Immunomodulation; Mesenchymal stem cells; Umbilical cord; Xenogeneic mouse model.