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

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

Xiaoyang Yuan #  1 , Xulei Wang #  1   2 , Tianxi Du  2 , Feng Zhang  1 , Gang Cheng  1 , Kang Wang  1 , Haochen Xu  1 , Pingting Yang  1 , Yan Chang  2 , Wei Wei  1 , Peng He  3 , Shangxue Yan  1   2
Affiliations

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

Xiaoyang Yuan et al. Front Bioeng Biotechnol. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
HE and immunohistochemical analyses of joint slices from different groups to evaluate the therapeutic effect of iPSC-MSCs.
FIGURE 2
FIGURE 2
Detecting the tracking sensitivity of biofluorescence imaging. (A) The fluorescent signal in serial cell dilutions. (B) The results of quantitative analysis of cellular fluorescence signals in vitro. (C) The fluorescence signals of rats injected with serial cell dilutions. (D) The results of quantitative analysis of fluorescence signals in vivo. **P < 0.01.
FIGURE 3
FIGURE 3
The metabolism of Antares2-iMSCs in the rat knee joint cavity. (A) The fluorescence signals were dynamically recorded in the sham-operated rats and the OA rats. (B) Quantified fluorescence intensity of the sham-operated and OA groups. (Values are presented as means ± sd.).
FIGURE 4
FIGURE 4
Tracking the distribution of iPSC-MSCs in joints. (A) Fluorescence imaging of synovial, meniscal and cartilage tissues in the joint cavity of rats in the sham-operation group. (B) Fluorescence intensity of synovium, meniscus and cartilage tissue in the sham-operation group. (C) Fluorescence imaging of synovial, meniscus and cartilage tissues in the joint cavity of rats in the OA group. (D) Fluorescence intensity of synovium, meniscus and cartilage tissue in the OA group. (E–G) Fluorescence intensity of synovial (E), meniscal (F) and cartilage (G) tissues in the sham-operated and OA groups.
FIGURE 5
FIGURE 5
The expression of CD90/Thy protein in the synovium of rat joint cavities.
FIGURE 6
FIGURE 6
Detection of CD90 (iPSC-MSCs) expression levels in synovial fluid by flow cytometry.
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