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诱导多能干细胞来源的间充质干细胞在骨关节炎大鼠模型关节腔内的分布与代谢

Distribution and metabolism of iPSC-MSCs in the joint cavity of an osteoarthritis rat model.

作者信息

Yuan Xiaoyang, Wang Xulei, Du Tianxi, Zhang Feng, Cheng Gang, Wang Kang, Xu Haochen, Yang Pingting, Chang Yan, Wei Wei, He Peng, Yan Shangxue

机构信息

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.

Laboratory Animal Center, Anhui Medical University, Hefei, China.

出版信息

Front Bioeng Biotechnol. 2025 Jun 17;13:1555983. doi: 10.3389/fbioe.2025.1555983. eCollection 2025.

DOI:10.3389/fbioe.2025.1555983
PMID:40599407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12209229/
Abstract

INTRODUCTION

To investigate the metabolism and distribution of iPSC-MSCs in the joint cavity of rats with knee osteoarthritis (KOA).

METHODS

The iPSC-MSCs labeled with the Antares2 luciferase gene were injected into the knee joints of rats, and then the metabolism and distribution of the cells in vivo were revealed by imaging and molecular biomarker methods.

RESULT

Histopathological results demonstrated that iPSC-MSCs significantly reversed joint tissue damage of arthritic rats. The fluorescence signal of iPSC-MSCs labeled with Antares2 luciferase gene was stable and persistent with high detection sensitivity. The fluorescent signal duration of Antares2-iMSCs in the joint cavity of KOA rats was approximately 2 weeks, which was significantly longer than 1 week in the sham-operated group. The proportion of iPSC-MSCs in the synovial fluid gradually decreased over time, and for the first time, the cells were observed to attach to the synovium first, followed by the meniscus and cartilage.

DISCUSSION

This study was the first to explore the metabolism and distribution of iPSC-MSCs after intra-articular injection by labeling the Antares2 luciferase gene, which provides assurance and theoretical basis for the safety of clinical application of iPSC-MSCs in treating osteoarthritis.

摘要

引言

研究诱导多能干细胞来源的间充质干细胞（iPSC-MSCs）在膝骨关节炎（KOA）大鼠关节腔内的代谢及分布情况。

方法

将标记有Antares2荧光素酶基因的iPSC-MSCs注入大鼠膝关节，然后通过成像和分子生物标志物方法揭示细胞在体内的代谢及分布。

结果

组织病理学结果表明，iPSC-MSCs显著逆转了关节炎大鼠的关节组织损伤。标记有Antares2荧光素酶基因的iPSC-MSCs荧光信号稳定持久，检测灵敏度高。KOA大鼠关节腔内Antares2-iMSCs的荧光信号持续时间约为2周，明显长于假手术组的1周。iPSC-MSCs在滑液中的比例随时间逐渐降低，首次观察到细胞先附着于滑膜，其次是半月板和软骨。

讨论

本研究首次通过标记Antares2荧光素酶基因探索关节腔内注射后iPSC-MSCs的代谢及分布，为iPSC-MSCs治疗骨关节炎临床应用的安全性提供了保障和理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/6d37a76ebbcb/fbioe-13-1555983-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/da2b0d805bf0/fbioe-13-1555983-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/6738d6c16362/fbioe-13-1555983-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/2099484e8f69/fbioe-13-1555983-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/f6cfd29a42fd/fbioe-13-1555983-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/1bcf905f63be/fbioe-13-1555983-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/6d37a76ebbcb/fbioe-13-1555983-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/da2b0d805bf0/fbioe-13-1555983-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/6738d6c16362/fbioe-13-1555983-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/2099484e8f69/fbioe-13-1555983-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/f6cfd29a42fd/fbioe-13-1555983-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/1bcf905f63be/fbioe-13-1555983-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6fd/12209229/6d37a76ebbcb/fbioe-13-1555983-g006.jpg

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The iPSC secretome is beneficial for in vitro propagation of primary osteoarthritic chondrocytes cell lines.
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