Organoids: Types, Studies and Ethical Use

Author: Disabled World - Contact Details
Updated/Revised Date: 2022/10/09
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Synopsis: Information, trial reports, and studies using organoids to study diseases, drug screening, and delivery methods and to advance personalized human medicine. Organoids are an emerging technique developed in the last decade or so for the 3D culture of primary cells, typically adult stem cells or pluripotent stem cells, in a microscale structure that mimics the natural organization of cells within a tissue - Encyclopedia of Infection and Immunity. With the advent of human organoids - stem cell-derived 3D culture systems - it is now possible to re-create the architecture and physiology of human organs in remarkable detail.



The term "Organoid" was coined in the Netherlands about ten years ago by Professor Hans Clevers, who was then an important researcher in stem cell research. Lancaster and Knoblich define an organoid as a collection of organ-specific cell types that develops from stem cells or organ progenitors, self-organizes through cell sorting and spatially restricted lineage commitment like in vivo, and exhibits the following properties:

  • It has multiple organ-specific cell types.
  • Its cells are grouped together and spatially organized, similar to an organ.
  • It can recapitulate some specific organ functions (e.g. contraction, neural activity, endocrine secretion, filtration, excretion).

The use of organoids have already found application in areas such as developmental biology, regenerative medicine, disease modeling, drug discovery, and personalized medicine.

Main Document

What are Organoids?

Organoids provide ways of culturing organ-specific tissue from stem cells that could change how diseases are studied and treated by permitting researchers to observe how organ structures emerge in early human development and how certain genetic mutations or infections can derail an organ's function. "You can watch as a congenital defect unfolds before your eyes in the dish," says James Wells, a developmental biologist at Cincinnati Children's Hospital Medical Center in Ohio.

While research on stem cells and regulation of stemness was the first field of application of intestinal organoids, they are now used to study the uptake of nutrients, drug transport, and secretion of incretin hormones. This is relevant in malabsorption and metabolic diseases such as obesity, insulin resistance, and diabetes. Organoids provide a promising tool to advance personalized medicine and next-generation drug screening and to limit the need for animal experimentation.

Partial List of Current Organoids Includes:

There are potential as many types of organoids as there are different tissues and organs in the body. To date, researchers have been able to produce organoids that resemble the:

  • Blastoid (blastocyst-like organoid)
  • Blood-brain barrier (BBB) organoid
  • Brain
  • Cardiac organoid
  • Colon
  • Epithelial organoid
  • Gastruloid (embryonic organoid)
  • Glioblastoma
  • Heart
  • Hepatic organoid
  • Inner ear
  • Intestine
  • Kidney
  • Liver
  • Lung
  • Mammary and salivary glands
  • Nasal
  • Ovary
  • Pancreas
  • Prostate
  • Retinal
  • Small intestine
  • Spinal organoids
  • Stomach
  • Testicular
  • Thymic organoid
  • Thyroid

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Human cerebral organoids are small balls of human brain cells ranging in size from a poppy seed to a small pea. This photo is a Brightfield microscope image of an organoid during development, showing highly structured regions forming - Image Credit: National Institute of Allergy and Infectious Diseases, NIH.
Human cerebral organoids are small balls of human brain cells ranging in size from a poppy seed to a small pea. This photo is a Brightfield microscope image of an organoid during development, showing highly structured regions forming - Image Credit: National Institute of Allergy and Infectious Diseases, NIH.

Brain Organoid Example

Human brain organoids (HBOs), also known as human cerebral organoids, are small balls of human brain cells ranging in size from a poppy seed to a small pea. Their organization, structure, and electrical signaling are similar to brain tissue. Because these cerebral organoids can survive in a controlled environment for months, nervous system diseases can be studied over time. Cerebral organoids have been used as models to study Zika virus infection, Alzheimer’s disease, Down syndrome, and autism spectrum disorders (ASD).

A cerebral organoid, or brain organoid, describes an artificially grown, in vitro, miniature organ resembling the brain and is a self-organizing three-dimensional tissue derived from human embryonic stem cells or pluripotent stem cells can simulate the architecture and functionality of the human brain. Some liberal theories of consciousness, such as IIT and panpsychism, allow even those underdeveloped brain organoids to have a primitive form of consciousness.

Studying Neuropsychiatric / Neurodevelopmental Diseases:

Research on organoids made up of human cell material has the advantage that the findings are transferable to humans. They can be used to study not only basic developmental biology but also the role of genes in diseases or developmental brain disorders. Research scientists are currently working with organoids of this type to investigate the genetic cause of autism and heterotopia.

Some of the most prominent neuropsychiatric or neurodevelopmental diseases of our time, such as schizophrenia or autism spectrum disorder, are uniquely human diseases that affect the whole human genome. Among many other studies, cerebral organoids are used to study autism spectrum disorders. In one study, cerebral organoids were cultured from cells derived from macrocephaly ASD patients. These cerebral organoids were found to reflect characteristics typical of the ASD-related macrocephaly phenotype in the patients. Cultivating cerebral organoids from ASD patients with macrocephaly could make connections between certain gene mutations and phenotypic expression. The significance of this use of brain organoids for autism studies is that it has added great support for the excitatory/inhibitory imbalance hypothesis, which, if proven true, could help identify targets for drugs so that the condition could be treated.

Creating Organoids

All organoids begin as stem cells, grown in precise culture conditions that make them differentiate into multiple cell types that self-organize and cooperate. Stem cells used for organoid creation include tissue-derived adult stem cells (ASCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and patient-derived tumor tissue cells.

Organoids can range in size from less than the width of a hair to five millimeters. Currently, organoids don't develop beyond these tiny and simplistic models of organs. They lack features that allow real organs to function and grow, notably, a system of blood vessels that nourish internal tissue as the organ gets bigger.

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The image shows a plate with testing chambers containing kidney organoids generated by robots from human stem cells. The different colors mark distinct segments of the kidney - Image Credit: University of Washington Photo - Freedman Lab.
The image shows a plate with testing chambers containing kidney organoids generated by robots from human stem cells. The different colors mark distinct segments of the kidney - Image Credit: University of Washington Photo - Freedman Lab.

Organoid Growth Kits

Reliably generate, expand, and differentiate physiologically relevant human organoids. Organoid growth kits make it easy to subculture and grow your patient-derived organoids. Add the kit's contents into your basal and conditioned medium, and you're ready to feed your organoids. For example, one U.S. company, American Type Culture Collection (ATCC), has developed Organoid Growth Kits which comprise single-use supplements created to streamline media preparation.

Organoid growth kits contain the most costly and cumbersome supplements and reagents, reducing the time and effort required to prepare media and ensuring the successful growth of your organoids. ATCC CoreKits are packages of recombinant proteins, small molecules, and other supplements designed to prepare complex media formulations for select organoid culture models easy and reliable.

Technical Issues

Compared with traditional 2D culture systems, 3D organoids better resemble the native organ in terms of gene and protein expression, metabolic function, and microscale tissue architecture. They have a huge potential for applications linked to human health. They can be used for regenerative medicine, as you can expand human material from just a small biopsy. Organoids are invaluable preclinical models for studying cancer and offer many advantages over human or non-human animal cancer models.

Despite the promising features of organoids, their broad utility is tempered by various limitations yet to be overcome, including lack of high-fidelity cell types, limited maturation, atypical physiology, and lack of realization, which may limit their reliability for certain applications. Organoids promise greater representation of our tissues than cell lines but offer reduced complexity compared to tissue explants or animal models.

The widespread and increasing adoption of organoid-based technologies in human biomedical research is a testament to their enormous potential in basic, translational, and applied research. Similarly, there appear to be ample possibilities for future research applications of organoids from livestock to companion animals.

Ethical Concerns

Organoids are not seen by some as morally neutral. For instance, tissue donors may perceive enduring personal connections with their organoids, setting higher bars for informed consent and patient participation. Brain organoids and human-animal chimeric organoids have also raised controversy. Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids partially recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities.

Despite the promises for science, the technology of organoids continues to pose complex ethical challenges because it involves the use of human tissues, human stem cells, production of sensitive personal data, long-term storage in biobanks, as well as the potential for some organoids to obtain human characteristics.

The brain is considered the source of our consciousness. Therefore, if brain organoids truly mimic the brain, they, too, should develop a consciousness that brings all sorts of moral implications. We believe a precautionary principle should be taken as neither science nor philosophy can agree on whether something has consciousness. Instead of arguing whether brain organoids have consciousness, decide they do as a precaution and consider moral implications.

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