Browsing by Author "Cha, Juyeon"

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    Induced pluripotent stem cells (iPSCs) as a cellular therapy for post-traumatic osteoarthritis in a murine model
    (2024-12-18) Cha, Juyeon; Krawetz, Roman; Chu, Li-Fang (Jack); Salo, Paul Timothy
    Stem cell therapy holds promise in treating various diseases including the degenerative joint disease known as osteoarthritis (OA). Yet, it is essential to obtain a homogenous cell population in clinically relevant numbers for these therapies. In this study, I scaled-up iPSC culture in suspension bioreactors and then transplanted these cells into the knee joints of mice with OA. I characterized the pluripotency of bioreactor cultured iPSCs using flow cytometry, immunofluorescence, proteomics, and teratoma assay. For in vivo experiments, non-invasive ACL rupture was induced to initiate post-traumatic osteoarthritis (PTOA) in C57BL/6 mice. Post-injury, 5.0x104 iPSCs were intra-articularly injected into the injured knee (N=12), and control animals were injected with DPBS (N=12). To eliminate risk of tumorigenesis, iPSCs expressed the iCaspase9 suicide gene system, which induces apoptosis upon injection of a chemically induced dimerizer (CID). Five days after cell injection, mice were subjected to daily administration of CID for 5 days. Outcomes were measured using histology and gait analysis. Molecular and functional assessment of pluripotency demonstrated that bioreactor grown iPSCs maintained their phenotype during and after the bioprocess. Mice post-ACL rupture treated with iPSCs showed no significant differences in histology compared to the vehicle alone control animals. Gait analysis demonstrated alleviation in gait imbalance after 4 weeks from inducing OA in both iPSC treated and control groups. However, iPSC-treated mice restored gait balance closer to baseline by week 8, compared to control mice. These results demonstrate that iPSCs can be successfully scaled up in bioreactors under controlled conditions and that they offer potential as a therapeutic strategy for PTOA, providing insights for the development of safe and effective iPSC-based cell therapies.