ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1555983
Distribution and metabolism of iPSC-MSCs in the joint cavity of an osteoarthritis rat model
Provisionally accepted
Xiaoyang Yuan1Xulei Wang1,2
Tian Xi Du2Feng Zhang1Gang Cheng1Kang Wang1Haochen Xu1Pingting Yang1
Yan Chang1
Wei Wei1Peng He3*
Shangxue Yan1,2*- 1Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
- 2Laboratory Animal Center, Anhui Medical University, Hefei, Anhui Province, China
- 3Department of Orthopedics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
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Preliminary study results show induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs), exhibit promising efficacy in an osteoarthritis rat model. However, the pharmacokinetics of iPSC-MSCs after injection into the knee joint are unknown, which limits further clinical applications.. The aim of this study was to investigate the therapeutic effects， the metabolism and distribution of iPSC-MSCs in the joint cavity of rats with knee osteoarthritis (KOA). 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. Histopathological results demonstrated that iPSC-MSCs significantly reversed joint tissue damage of arthritic rats. The fluorescence signal of iPSC-MSCs labeled with the 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. In conclusion, 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 a theoretical basis for the safety of clinical application of iPSC-MSCs in treating osteoarthritis.
Keywords: iPSC-MSCs, Antares2-iMSCs, Osteoarthritis, Metabolism, biodistribution
Received: 10 Jan 2025; Accepted: 04 Jun 2025.
Copyright: © 2025 Yuan, Wang, Du, Zhang, Cheng, Wang, Xu, Yang, Chang, Wei, He and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Peng He, Department of Orthopedics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
Shangxue Yan, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
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