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

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

doi:10.3389/fbioe.2025.1555983

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

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

Authors

Xiaoyang Yuan^#¹, Xulei Wang^#^{1

2}, Tianxi Du², Feng Zhang¹, Gang Cheng¹, Kang Wang¹, Haochen Xu¹, Pingting Yang¹, Yan Chang², Wei Wei¹, Peng He³, Shangxue Yan^{1

2}

Affiliations

¹ Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
² Laboratory Animal Center, Anhui Medical University, Hefei, China.
³ Department of Orthopedics, First Affiliated Hospital of Anhui Medical University, Hefei, China.

^# Contributed equally.

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.

Keywords: Antares2-iMSCs; biodistribution; iPSC-MSCs; metabolism; osteoarthritis.