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Table 1 Establishment of organoids will greatly benefit from a figure and/or table summarizing the different types of organoids, references to protocols of establishing them, advantages/disadvantages of each system etc.

From: 3D and organoid culture in research: physiology, hereditary genetic diseases and cancer

Type of organoid

Cell source

Achievements

Protocol to establish them

Intestine

ASC (intestinal crypt Lgr5+ stem cells)

• Faithfully recapitulates the tissue

• Long term growth

• Growth of mouse adenomas, human colorectal cancer cells, and human metaplastic epithelia

[82, 84]

iPSC

• The presence of mesenchymal cells leads to less niche factor requirements

• Cost-effective

[85]

ESC

• The epithelium contains functional enterocytes, as well as goblet, Paneth and enteroendocrine cells

[45]

Stomach

ASC (gastric epithelium Lgr5+ stem cells/TROY+ chief cells)

• Long-term growth

• Robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells

[87]

[89, 90]

PSC

• Primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and diversity of gastric endocrine cells

[88]

Liver

ASC (Lgr5+ stem cells/ mature hepatocytes)

• Long-term growth

• Cells can be converted into functional hepatocytes in vitro and upon transplantation into mice

• Recapitulates the proliferative damage-response of hepatocytes

[35, 95]

iPSC

• Cells in organoids differentiate into functional hepatocytes and cholangiocytes

• The organoids organize a functional bile canaliculi system, which is disrupted by cholestasis-inducing drugs

[52]

ESC

• Scalable culture system with a high level of recapitulation of the liver-specific microenvironment

• Efficient hepatic maturation upon ex ovo transplantation

[229]

Pancreas

ASC (Lgr5+ stem cells)

• The organoid recapitulates the morphology, the epithelial polarization and the genomic stability of their origin tissue

[96]

iPSC

• The organoids present an appropriate marker profile and ultrastructural, global gene expression and functional hallmarks of the human pancreas

• Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas

[230]

ESC

• Functional alpha, beta, delta, and polypeptide cells, and ability to secrete insulin-secretory granules

[76, 77]

Lung

ASC (basal cells, Clara cells and specialized alveolar type II cells (AEC2s))

• “Tracheospheres” derived from basal cells generate both secretory and ciliated cells

• “Alveolospheres” derived from AEC2s cells contain both AEC2 and AEC1 present in the alveoli

[99, 100]

[102]

iPSC

• The organoids possess upper airway-like epithelium with basal cells and immature ciliated cells surrounded by smooth muscle and myofibroblasts as well as an alveolar-like domain with appropriate cell types

• The cultures could be maintained for several months

[43, 53]

ESC

• They include epithelial and mesenchymal cells and are able to produce surfactant

[43]

Brain

iPSC

• The organoids recapitulate progenitor zone organization, neurogenesis, gene expression, and a distinct human-specific outer radial glia cell layer

• Co-culture of different parts of the brain can recreate the dorsal–ventral forebrain axis

[57, 60]

ESC

• Generation of multiple organoids from different parts of the brain (midbrain, forebrain)

• Electrically active and functionally mature neurons with dopamine production

• In-vitro functional vasculature-like networks to increase the maturation of the organoid

[63, 78,79,80]

Retina

iPSC

• Retinal cups contain all major retinal cell types arranged in their proper layers

• Their photoreceptors achieve advanced maturation, showing the beginning of outer-segment disc formation and photosensitivity

[115]

ESC

• Fully stratified retinal tissue consisting of all major neural retinal components

[112, 113]