| 발표일자: |
2019년 11월 1일(금)~3(일) |
| 발표번호: |
P(e-poster)-269 |
| 발표장소: |
B3 Parking Area
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| 유효한 면역조절 기능을 가진 중간엽 줄기세포 유래 엑소좀 소포의 분자 프로파일 분석 |
| 한림대학교 의과대학, 한림대학교 성심병원 안과(1), Texas A&M University, College of Medicine, 재생의학연구소(2), 서울대학교병원 의생명연구원 인공안구센터 안면역각막재생연구실(3), Baylor College of Medicine, 분자세포생물학과(4), 서울대학교병원 안과학교실(5) |
| 이민정(1), 김혜미(2), 배은해(1), 류진숙(3), 김현지(3), 김준엽(3), Heather Barreda(2), 정성연(4), 최종민(4), Taeko Shigemoto-Kuroda(1), 이량화(1), 오주연(3,5) |
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목적 : To identify a molecular profile of functionally effective mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) in immunomodulation.
방법 : We compared immunomodulatory effects 1) between EV derived from early (passage 2, P2)- vs late passage (passage 7, P7) mesenchymal stem cells (MSCs) and 2) between EV derived two dimensional cultures of P2 MSCs vs three dimensional cultures of P2 MSCs in 1) cultures of splenocytes stimulated by LPS and 2) a mouse model of lacrimal gland inflammation and dry eye. In parallel, we performed proteomics, RNA sequencing, and microRNA array and compared between EVs.
결과 : P2 EVs were more effective in improving tear production and corneal surface integrity and suppressing lacrimal gland inflammation than P7 EVs. Activation of LPS-stimulated splenocytes was also more significantly reduced by P2 EVs. Similarly, 3D P2 EVs were better in suppressing splenocyte activation than 2D P2 EVs. Comparative molecular profiling identified the enriched factors in 3D cultured P2 EVs, of which TGFβ1, PTX3 (pentraxin 3) and let-7b-5p showed prominent expression. Inhibition or overexpression of TGFβ1, PTX3 or let-7b-5p in MSCs significantly abrogated or promoted the immunomodulatory effects of their EVs.
결론 : Identification of distinctive molecular profiles of MSC-EVs effective in immunomodulation would help understand the molecular mechanisms underlying the EV-mediated immunomodulation. The identified factors can be used as biomarkers for functional EV production.
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