(F1032) COMPARISON OF MULTICELLULAR HEPATIC ORGANOID DIFFERENTIATION USING DIFFERENT CULTURE SYSTEMS AND INDUCED PLURIPOTENT STEM CELLS DERIVED FROM VARIOUS CELL SOURCES
Student Catholic University of Korea Catholic University of Korea, Republic of Korea
Abstract: Stem cell-derived hepatic organoids are widely used across various research fields; however, current differentiation techniques face several limitations, including low efficacy, insufficient maturity, and challenges in replicating the in vivo microenvironment within an in vitro three-dimensional (3D) structure. Addressing these challenges requires careful selection of both the primary cell source and the culture system to optimize organoid differentiation from human induced pluripotent stem cells (hiPSCs). hiPSCs can be derived from various primary cells, such as blood cells, keratinocytes, and urine cells. However, differences in gene expression patterns, epigenetic modifications, and differentiation potential of primary cells influence their subsequent differentiation tendencies. Additionally, the choice of culture system plays a crucial role in shaping the growth environment and supporting the structural and functional development of organoids. For instance, 3D culture systems significantly influence the differentiation of specific cell types, including neurons, hepatocytes, and cardiac cells. In this study, hiPSCs were generated from cord blood mononuclear cells and differentiated into multicellular liver organoids (mHOs) under three experimental conditions: 1) without Matrigel, 2) with Matrigel added to the culture medium, and 3) embedded within a Matrigel dome. Additionally, hiPSCs derived from dermal fibroblasts and peripheral blood mononuclear cells were differentiated into mHOs. The findings reveal that both the choice of primary cell source and the culture conditions significantly affect the differentiation and development of hepatic organoids.
Funding Source: This work was supported by the National Research Foundation of Korea (NRF) and ministries including Science and ICT, Trade, Industry and Energy, Health & Welfare, and Food and Drug Safety (RS-2023-KH142779, RS-2024-00512348).
