Small Molecules for Organoid Culture

Human brain and neural organoids are established through the differentiation induction of human pluripotent stem cells (hPSCs), rather than from primary neural cells or excised tissues, due to experimental and ethical constraints. This approach enables in vitro recapitulation of the diverse neural cell populations and highly organized three-dimensional structures characteristic of the developing human brain.

Compared with animal models such as rodents, human brain organoids more faithfully reproduce human-specific mechanisms of central nervous system development, neuronal circuit formation, and the pathophysiology of neurodevelopmental disorders.They serve as highly valuable pathological models for conditions including autism spectrum disorder, schizophrenia, and neurodevelopmental disorders associated with Zika virus infection.

Small Molecules for Brain and Neural Organoid Generation

References

1. Lancaster, MA., et al. : Nature., 501, 373 (2013).
2. Pollen, AA., et al. : Cell., 176, 743 (2019).
3. Huang, WK., et al. : Cell Stem Cell., 28, 1657 (2021).
4. Smits, LM., et al. : NPJ Parkinson's Dis., 5, 5 (2019).
5. Suong, DNA., et al. : Commun. Biol., 4, 1213 (2021).

Lung organoids are three-dimensional (3D) culture models used to study human lung development, viral infections— including severe acute respiratory syndrome (SARS), the 2009 pandemic influenza A (H1N1), and Middle East respiratory syndrome (MERS) —and respiratory diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease (COPD). They are also employed to investigate the effects of air pollution and smoking.

Unlike conventional immortalized cell lines or primary lung cells, lung organoids comprise multiple differentiated cell types and more accurately recapitulate the complex architecture and functions of lung tissue. Lung organoids can be established from small amounts of patient-derived tissue or from pluripotent stem cells and are expected to contribute to advances in personalized medicine and the development of disease-specific biobanks.

Small Molecules for Lung Organoid Generation

References

1. Tamai, K., et al. : Cell Rep Methods., 2, 100314 (2022).
2. Kakizaki, M., et al. : J Virol.,99, e01853 (2024).
3. Hashimoto, R., et al. : Life Sci Alliance., 8, e202402837 (2025).

Cardiac organoids are functional three-dimensional in vitro models of the heart.
Advances in microgravity culture and on-chip manipulation technologies have enabled the generation of more mature cardiac tissue, facilitating applications in drug screening, disease modeling, and personalized medicine.

Small Molecules for Cardiac Organoid Generation

• CHIR99021
• IWP-2
• IWR-1
• all-trans-Retinoic Acid
• Y-27632

References

1. Moriwaki, T., et al. Cell Rep Methods., 3, 100666 (2023).
2. Drakhlis, L., et al. Nat. Biotechnol., 39, 737 (2021).

Liver organoids are functional three-dimensional in vitro models of the liver.
They comprise not only hepatocytes but also vascular and other supporting cell types, which self-organize to form three-dimensional structures and recapitulate key liver functions such as detoxification and metabolism.

Liver organoids are widely used in research on liver development, regeneration, detoxification, metabolism, and liver disease modeling.

Small Molecules for Liver Organoid Generation

• A-83-01
• CHIR99021
• DAPT
• Dexamethasone

References

1. Reza, HA., et al. Stem Cell Reports., 18, 2071 (2023).
2. Ueyama-Toba, Y., et al. iScience., 27, 110778 (2024).

Pancreatic organoids are functional three-dimensional in vitro models of the pancreas.They contain pancreas-specific cell types, including ductal cells and progenitor cells, and recapitulate key functions such as digestive enzyme secretion and hormone production.

Pancreatic organoids are used to study pancreatic development, investigate diseases including diabetes and pancreatic cancer, and support drug screening.

Small Molecules for Pancreas Organoid Generation

• CHIR99021
• TTNPB

References

1. Kimura, A., et al. : Stem Cell Res., 24, 61 (2017).
2. Toyoda, T., et al. : Stem Cell Res., 14, 185 (2025).

Kidney organoids are functional three-dimensional in vitro models of the kidney.
They recapitulate key kidney features, including nephron structures, vascular networks, and interstitial components.

Kidney organoids are utilized for kidney disease modeling, studies of kidney development, and screening of nephrotoxic compounds. They are also emerging as valuable tools for developing therapies for chronic kidney disease (CKD), a major global health challenge.

Small Molecules for Kidney Organoid Generation

References

1. Kuraoka, S., et al. : J. Am. Soc. Nephrol., 31, 2355 (2020).
2. Hirayama, R., et al. : Commun Biol., 6, 854 (2023).

Intestinal organoids are functional three-dimensional in vitro models of intestinal tissue.
Since the first report of a mouse small intestinal organoid model in 2009, methods for culturing mouse colonic organoids as well as human small intestinal and colonic organoids, have been established. Intestinal organoids are now widely used in early drug discovery, patient-specific drug screening, oncology and immunology research, and studies of infectious disease pathogenesis.

Small Molecules for Intestinal Organoid Generation

References

1. Zhang, RR., et al. : Stem Cell Reports., 10, 780 (2018).
2. Ogawa, I., et al. : Biol Open, 14, bio061612 (2025).