Preconditioning with interleukin-1 beta and interferon-gamma enhances the efficacy of human umbilical cord blood-derived mesenchymal stem cells-based therapy via enhancing prostaglandin E2 secretion and indoleamine 2,3-dioxygenase activity in dextran sulfate sodium-induced colitis
Yeonsil Yu
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSae Mi Yoo
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorHwan Hee Park
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSong Yi Baek
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorYoon-Jin Kim
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSeunghee Lee
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorYu Lee Kim
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Kwang-Won Seo
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Correspondence
Kwang-Won Seo and Kyung-Sun Kang, Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University. Seoul 08826, South Korea.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Kyung-Sun Kang
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
Correspondence
Kwang-Won Seo and Kyung-Sun Kang, Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University. Seoul 08826, South Korea.
Email: [email protected]; [email protected]
Search for more papers by this authorYeonsil Yu
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSae Mi Yoo
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorHwan Hee Park
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSong Yi Baek
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorYoon-Jin Kim
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorSeunghee Lee
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorYu Lee Kim
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Kwang-Won Seo
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Correspondence
Kwang-Won Seo and Kyung-Sun Kang, Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University. Seoul 08826, South Korea.
Email: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Kyung-Sun Kang
Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University, Seoul, South Korea
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea
Correspondence
Kwang-Won Seo and Kyung-Sun Kang, Stem Cell and Regenerative Bioengineering Institute, Kangstem Biotech Co., Ltd., Biotechnology Center, Seoul National University. Seoul 08826, South Korea.
Email: [email protected]; [email protected]
Search for more papers by this authorAbstract
Preconditioning with inflammatory cytokines has improved mesenchymal stem cells characteristics, including differentiation and immunomodulating functions. In this study, we developed a preconditioning combination strategy using interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) to enhance the immuneregulatory ability of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Our results showed that hUCB-MSCs preconditioned with IL-1β and IFN-γ (primed hUCB-MSCs) created a statistically significant decrease in peripheral blood mononuclear cell proliferation, indicating that their immunosuppressive ability was increased. The secretion of PGE2, cyclooxygenase 2 mRNA expression, and indoleamine 2,3-dioxygenase (IDO) mRNA expression in primed hUCB-MSCs was significantly higher than those in the untreated hUCB-MSCs or the IL-1β or IFN-γ only treated hUCB-MSCs. When inhibitors of IDO and PGE2 were treated, peripheral blood mononuclear cell proliferation, which is inhibited by primed hUCB-MSCs, was recovered. We found that Th1 T cell differentiation was also inhibited by PGE2 and IDO in the primed hUCB-MSCs, and Tregs differentiation was increased by PGE2 and IDO in the primed hUCB-MSCs. Furthermore, the primed hUCB-MSCs as well as supernatants increase CD4+ T cells migration. We demonstrated the therapeutic effects of primed hUCB-MSCs in dextran sulfate sodium-induced colitis model. In conclusion, we have demonstrated that primed hUCB-MSCs simultaneously enhance PGE2 and IDO and greatly improve the immunoregulatory capacity of MSCs, and we have developed an optimal condition for pretreatment of MSCs for the treatment of immune diseases. Our results raise the possibility that the combination of PGE2 and IDO could be therapeutic mediators for controlling immunosuppression of MSCs.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interests regarding the publication of this paper.
Supporting Information
| Filename | Description |
|---|---|
| term2930-supp-0001-supp_info.docxWord 2007 document , 13.9 KB | Data S1. Supplementary information |
| term2930-supp-0002-supp_info.docxWord 2007 document , 409.3 KB |
Table S1. Microarray Analysis Figure S1. Characterization of hUCB-MSCs under the stimulation of IFN-γ and IL-1β. MSCs were culture with or without IFN-γ and IL-1β for 24 h. (a) Differentiation capacity of unstimulated, IFN-γ and IL-1β stimulated MSCs into adipocytes, osteoblasts and chondroblasts. (b) The expression of immunophenotypic surface antigens on MCS was detected by flow cytometric analysis. Figure S2. Colon length in different DSS concentration. We have tested 3%, 4% and 5% DSS to induce colitis and confirmed severe symptoms by observing shorted colon lengths in the 4% and 5% DSS treated groups. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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