R&D Team Manager / Researcher KarisBio Inc Seoul, United States
Abstract: Human induced pluripotent stem cells (hiPSCs) hold immense potential for regenerative medicine, particularly in treating ischemic cardiovascular and neurodegenerative diseases. Despite their promise, the clinical translation of hiPSCs and/or hiPSC-derived cell therapy (CT) products has been hindered by challenges associated with the inherent characteristics of hiPSCs such as the tumorigenic potential. Indeed, the presence of a small amount of unexcluded hiPSCs may pose safety risks particularly if they are retained within unintended parts of the body. To address the challenges for CT products before human application, biodistribution studies serve as a critical component of preclinical safety and toxicity evaluations. Quantitative methods based on PCR techniques have been developed and widely applied for biodistribution assessment, offering high specificity, sensitivity, and absolute quantification. Yet, due to the unique diversity and complexity of every biological therapy product’s characteristic, procedural considerations may vary, and regulatory guidance may not clearly suggest detailed, standardized criteria for all. As a result, direct implementation of a simple, universal approach is limited. In this study, we compile and summarize key guidance documents issued by regulatory authorities worldwide. Next, we propose a fit-for-purpose framework for establishing GLP-compliant biodistribution evaluation process for hiPSC-derived CT products. This framework consists of four essential steps: (1) study design of biodistribution assessment; (2) qPCR assay development; (3) assay validation; and (4) data analysis and interpretation. We further demonstrate the application of this framework conducting a biodistribution study of hiPSC-derived endothelial cells (hiPSC-ECs) in BALB/c nude mice, confirming its feasibility and suitability. We found that intramuscularly injected hiPSC-ECs were undetectable in 13 organs, excluding the injection site, after 12 hours post-injection across 86 animals distributed into 11 experimental groups. By providing a structured and practical approach to biodistribution assessment, our fit-for-purpose framework offers a clear path forward for advancing the development of safe, effective, and standardized hiPSC-derived therapies.
Funding Source: This work was supported by grants from the National Research Foundation of Korea funded by the Korean government (RS-2024-00509295), and Korea National Institute of Health research project (2023ER130202 and 2023ER130102).
