Organoid

File:Intestinal organoid.PNG

Intestinal organoid grown from Lgr5+ stem cells.

An organoid is a three-dimensional organ-bud grown in vitro. The technique for growing organoids has rapidly improved since the early 2010s, and it was named by The Scientist as one of the biggest scientific advancements of 2013.

History

In 2008, Yoshiki Sasai and his team at RIKEN institute demonstrated that stem cells can be coaxed into balls of neural cells that self-organize into distinctive layers. In 2009 the Laboratory of Hans Clevers at Hubrecht Institute and University Medical Center Utrecht, The Netherlands showed that single LGR5 stem cells build crypt-villus structures in vitro without a mesenchymal niche.

In 2013, Madeline Lancaster at the Austrian Academy of Sciences established a protocol for culturing cerebral organoids derived from stem cells that mimic the developing human brain's cellular organization. In 2014, Artem Shkumatov et al. at the University of Illinois at Urbana-Champaign demonstrated that cardiovascular organoids can be formed from ES cells through modulation of the substrate stiffness, to which they adhere. Physiological stiffness promoted three-dimensionality of EBs and cardiomyogenic differentiation.

Takebe et al. demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). They suggested that the less mature tissues, or organ buds, generated through the self-organized condensation principle might be the most efficient approach toward the reconstitution of mature organ functions after transplantation, rather than condensates generated from cells of a more advanced stage

Types of organoids

• Cerebral organoid
• Thyroid organoid
• Intestinal Organoid
• Testicular Organoid
• Hepatic Organoid
• Pancreatic Organoid
• Gastric Organoid
• Epithelial Organoid
• Lung Organoid
• Kidney Organoid

Organoid models of disease

Organoids provide an opportunity to create cellular models of human disease, which can be studied in the laboratory to better understand the causes of disease and identify possible treatments. In one example, the genome editing system called CRISPR was applied to human pluripotent stem cells to introduce targeted mutations in genes relevant to two different kidney diseases, polycystic kidney disease and focal segmental glomerulosclerosis. These CRISPR-modified pluripotent stem cells were subsequently grown into human kidney organoids, which exhibited disease-specific phenotypes. Kidney organoids from stem cells with polycystic kidney disease mutations formed large, translucent cyst structures from kidney tubules. Kidney organoids with mutations in a gene linked to focal segmental glomerulosclerosis developed junctional defects between podocytes, the filtering cells affected in that disease. Importantly, these disease phenotypes were absent in control organoids of identical genetic background, but lacking the CRISPR mutations. These experiments demonstrate how organoids can be utilized to create complex models of human disease in the laboratory, which recapitulate tissue-level phenotypes in a petri dish.

For further reading

• Kelly Rae Chi (2015). Orchestrating Organoids. A guide to crafting tissues in a dish that reprise in vivo organs. The Scientist.
• Takebe, T., Enomura, M., Yoshizawa, E., Kimura, M., Koike, H., Ueno, Y., ... & Taniguchi, H. (2015). Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell stem cell, 16(5), 556-565. DOI:10.1016/j.stem.2015.03.004