CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis

IF 18 1区 医学 Q1 ENGINEERING, BIOMEDICAL Bioactive Materials Pub Date : 2025-01-24 DOI:10.1016/j.bioactmat.2025.01.019
Sunyoung Park , Yeo-Jun Yoon , Yongpyo Hong , Jianning Yu , Jae-Min Cho , Ye Jin Jeong , Haeun Yu , Hyorim Jeong , Hyunjin Lee , Seungyeon Hwang , Won-Gun Koh , Ji Yeong Yang , Kyung-A Hyun , Hyo-Il Jung , Jae-Yol Lim
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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.

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来源期刊
Bioactive Materials
Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
28.00
自引率
6.30%
发文量
436
审稿时长
20 days
期刊介绍: Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.
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