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Biomaterials, Jun 14 2024, 311 S0142-9612(24)00201-1 | https://doi.org/10.1016/j.biomaterials.2024.122667 CEACAM1-engineered MSCs have a broad spectrum of immunomodulatory functions and therapeutic potential via cell-to-cell interaction

Eunbi Yi ^a,c,1, Jinyoung Go^b,c,1, So Hyeon Yun ^a, Sang Eun Lee ^b,c, Jihye Kwak ^d, Seong Who Kim ^b,c*, Hun Sik Kim ^a,c*

^aDepartment of Microbiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

^bDepartment of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

^cStem Cell Immunomodulation Research Center (SCIRC), University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

^dBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam, Republic of Korea

¹These authors contributed equally to this work.

*Corresponding authors: Seong Who Kim, Hun Sik Kim

Abstract

Mesenchymal stem cells (MSCs) have garnered attention for their regenerative and immunomodulatory capabilities in clinical trials for various diseases. However, the effectiveness of MSC-based therapies, especially for conditions like graft-versus-host disease (GvHD), remains uncertain. The cytokine interferon (IFN)-γ has been known to enhance the immunosuppressive properties of MSCs through cell-to-cell interactions and soluble factors. In this study, we observed that IFN-γ-treated MSCs upregulated the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), associated with immune evasion through the inhibition of natural killer (NK) cell cytotoxicity. To co-opt this immunomodulatory function, we generated MSCs overexpressing CEACAM1 and found that CEACAM1-engineered MSCs significantly reduced NK cell activation and cytotoxicity via cell-to-cell interaction, independent of NKG2D ligand regulation. Furthermore, CEACAM1-engineered MSCs effectively inhibited the proliferation and activation of T cells along with the inflammatory responses of monocytes. In a humanized GvHD mouse model, CEACAM1-MSCs, particularly CEACAM1-4S-MSCs, demonstrated therapeutic potential by improving survival and alleviating symptoms. These findings suggest that CEACAM1 expression on MSCs contributes to MSC-mediated regulation of immune responses and that CEACAM1-engineered MSC could have therapeutic potential in conditions involving immune dysregulation.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-17)
연구진국내 연구진
분야 의약학 > 면역의학

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