Int J Stem Cells.  2024 May;17(2):120-129. 10.15283/ijsc24044.

Guidelines for Manufacturing and Application of Organoids: Liver

• Moon HR
• Mun SJ
• Kim TH
• Kim H
• Kang D
• Kim S
• Shin JH
• Choi D
• Ahn SJ
• Son MJ

• KMID: 2556231
• DOI: http://doi.org/10.15283/ijsc24044

Abstract

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

Keyword

Liver organoids; Quality standards; In vitro testing; Hepatotoxicity

Figure

• 

  Fig. 1 A schematic diagram of liver organoid generation, quality assessment, and applications. To unlock the potential of liver organoids for diverse biomedical applications, it is essential to standardize the processes for generating organoids and assess their quality in terms of liver-like phenotypes and functionality. hASCs: human adult stem cells, hPSCs: human pluripotent stem cells, iPSCs: induced pluripotent stem cell, ESCs: embryonic stem cells, DE: definitive endoderm, HE: hepatic endoderm, ECM: extracellular matrix, ALB: albumin, AAT: α1-antitrypsin.

• 

  Fig. 2 Representative morphologies of liver organoids derived from (A) human adult stem cells (hASCs) and (B) human pluripotent stem cells (hPSCs). (A) Micrograph of the hASC-derived liver organoids present a spherical morphology. (B) hPSC-derived liver organoids under growth conditions display a spherical feature (left), while their morphologies undergo transformation during differentiation conditions (right). Scale bars=500 μm.

Reference

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