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Bioact. Mater., Available online 24 January 2025 | https://doi.org/10.1016/j.bioactmat.2025.01.019
CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis
Sunyoung Park a,b,1, Yeo-Jun Yoon c,1, Yongpyo Hong c,2, Jianning Yu a,d,2, Jae-Min Cho c, Ye Jin Jeong c, Haeun Yu a, Hyorim Jeong b, Hyunjin Lee b, Seungyeon Hwang c, Won-Gun Koh e, Ji Yeong Yang a,b, Kyung-A Hyun a,f, Hyo-Il Jung a,b, Jae-Yol Lim c
aSchool of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seoul, 03722, Republic of Korea
bThe DABOM Inc., 50 Yonsei-ro, Seoul, 03722, Republic of Korea
cDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
dDepartment of Biomedical Laboratory Science, Yonsei University, 1 Yeonsedae-gil, Wonju, Gangwon-do, 26493, Republic of Korea
eDepartment of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seoul, 03722, Republic of Korea
fKorea Electronics Technology Institute (KETI), Seongnam, Gyeonggi-do, 13509, Republic of Korea
1The authors contributed equally to this work as co-first authors.
2These authors contributed equally to this work as co-second authors.
Corresponding authors: Hyo-Il Jung, Jae-Yol Lim
aSchool of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seoul, 03722, Republic of Korea
bThe DABOM Inc., 50 Yonsei-ro, Seoul, 03722, Republic of Korea
cDepartment of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
dDepartment of Biomedical Laboratory Science, Yonsei University, 1 Yeonsedae-gil, Wonju, Gangwon-do, 26493, Republic of Korea
eDepartment of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seoul, 03722, Republic of Korea
fKorea Electronics Technology Institute (KETI), Seongnam, Gyeonggi-do, 13509, Republic of Korea
1The authors contributed equally to this work as co-first authors.
2These authors contributed equally to this work as co-second authors.
Corresponding authors: Hyo-Il Jung, Jae-Yol Lim
Abstract
Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs). CD9-enriched (CD9+) EVs were then isolated from the sgBPC secretome concentrate using a dual microfluidic chip. Notably, CD9+ EVs demonstrated superior uptake by salivary epithelial cells compared to CD9-depleted (CD9-) EVs and total EVs. In vivo studies using a salivary gland (SG) obstruction mouse model and ex vivo studies in SG fibrosis organoids revealed that CD9+ EVs significantly enhanced anti-fibrotic effects over CD9- EVs and control treatments. The presence of miR-3162 and miR-1290 in CD9+ EVs supported their anti-fibrotic properties by downregulating ACVR1 expression. The chemical reprogramming culture method effectively expanded sgBPCs, enabling consistent and scalable EV production. Utilizing microfluidic chip-isolated CD9+ EVs and ductal delivery presents a targeted and efficient approach for anti-fibrotic SG regeneration.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-02-12)
- 국내 연구진
- 바이오·의료융합 > 다학제 융합/복합
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