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장인근In Keun Jang

LIFELIVER. Co., LTD

EBioMedicine, Volume 28, February 2018, Pages 261-273 | https://doi.org/10.1016/j.ebiom.2018.01.002 Enhanced Immunosuppressive Properties of Human Mesenchymal Stem Cells Primed by Interferon-γ

Kim, D.S.^a,b, Jang, I.K.^c, Lee, M.W.^a,b,*, Ko, Y.J.^a, Lee, D.-H.^c, Lee, J.W.^a, Sung, K.W.^a,*, Koo, H.H.^a,b,d,*, Yoo, K.H.^a,b,e

^aDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
^bStem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea
^cBiomedical Research Institute, LIFELIVER. Co., LTD., Yongin, Gyeonggi-do, South Korea
^dDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
^eDepartment of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, South Korea

^*Corresponding author

Abstract

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases owing to their immunosuppressive properties. In this study, we aimed to identify the effect of interferon (IFN)-γ priming on immunomodulation by MSCs and elucidate the possible mechanism underlying their properties for the clinical treatment of allogeneic conflicts. Infusion of MSCs primed with IFN-γ significantly reduced the symptoms of graft-versus-host disease (GVHD) in NOD-SCID mice, thereby increasing survival rate when compared with naïve MSC-infused mice. However, infusion of IFN-γ-primed MSCs in which indoleamine 2,3-dioxygenase (IDO) was downregulated did not elicit this effect. The IDO gene was expressed in MSCs via the IFN-γ-Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) pathway, and the infusion of IDO-over-expressing MSCs increased survival rate in an in vivo GVHD model, similar to infusion of IFN-γ-primed MSCs. These data indicate that IFN-γ production by activated T-cells is correlated with the induction of IDO expression in MSCs via the IFN-γ-JAK-STAT1 pathway, which in turn results in the suppression of T-cell proliferation. Our findings also suggest that cell therapy based on MSCs primed with IFN-γ can be used for the clinical treatment of allogeneic conflicts, including GVHD.

논문정보

형식Research article
게재일2018년 02월 (BRIC 등록일 2021-09-24)
연구진국내 연구진
분야 의약학 > 종양의학
피인용횟수60회 이상 인용된 논문

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