Organoids and their culture, which are expected to be the key to regenerative medicine
- Tokaihit
- May 9
- 7 min read
Updated: May 9
Regenerative medicine aims to treat various diseases by regenerating damaged tissues and organs. In recent years, research in this field has become more active, and one thing that has been attracting attention is "organoids." Organoids are tissues that are cultured three-dimensionally outside the body using stem cells, and are often described as miniature organs.
In this article, we will provide an overview of the types of organoids and their uses, and summarize the culture of organoids. We will also introduce culture equipment that is useful for organoid culture, so we hope you will read to the end.
table of contents
1. Basic overview of organoids
1-1) What are organoids?
As mentioned above, organoids are three-dimensional structures cultured outside the body using stem cells. As the name "organoid" combines "organ" and "oid," they have characteristics that mimic organs and tissues. Although they have not yet been able to fully reproduce their functions, they are highly anticipated as an alternative to animal models, and research into them has been accelerating in recent years.
1-2) Types of organoids
Many types of organoids are being researched and produced to suit the characteristics of organs and tissues. As research on each organoid progresses, many possibilities are expected beyond organ transplantation, such as use as diagnostics for drug screening and toxicity testing, elucidation of pathology, and development of research into drug discovery. In addition to organs such as the brain, heart, lungs, liver, and kidneys, organoids of tumors in each organ have also been created, and the number of organoid types will continue to increase in the future.
Brain Organoids
Since the creation of three-dimensional brain tissue (brain organoids) derived from human ES cells in 2008, it has become possible to reproduce neurogenesis outside the body, and this has been expected to lead to basic research to elucidate the process of neurogenesis, applied research targeting neurological diseases, and clinical applications such as drug discovery. As of 2024, brain organoids with complex neural circuits have been created, although they are still only millimeter-sized, and they may play a major role in research aimed at elucidating the brain.
On the other hand, as the brain structures that can be reproduced become more complex, ethical issues are being considered if the created brain begins to develop consciousness, and there seems to be a need for the establishment of guidelines and regulations.
Journal name: Cell Stem Cell
Cardiac Organoids
Organoids are also being created for the heart, which is another important organ after the brain. Like brain organoids, they are created from stem cells such as iPS cells, and are expected to be used as miniature models of the heart to elucidate cardiac diseases and regenerative medicine. In terms of function, while brain organoids are expected to reproduce emotions, thoughts, and memories, cardiac organoids are expected to reproduce pulsating functions such as blood circulation.
However, it is difficult to reproduce the electrophysiological characteristics of the heart during beating, and complete functional reproduction has not yet been achieved. Another challenge is the difficulty of reproducing the complex structures of the heart, such as the atria, ventricles, and valves, but active research is being conducted using biomaterials and microfluidic devices .
Journal name: Frontiers in Cell and Developmental Biology
Lung Organoids
Pulmonary organoids have the unique function of gas exchange and are characterized by their ability to evaluate interactions with the external environment. The lung has a complex branching structure, and research is progressing on organoids created for each of the bronchi and alveoli. As with other organoids, there are still incomplete parts in terms of reproducing functions, but there are hopes that they will be useful in research into infectious diseases such as COVID-19, and in elucidating the mechanisms of the development and progression of lung cancer.
Journal name: Cell Reports Methods
Liver organoids
The liver is the central organ of metabolism in the body, and has major metabolic functions such as drug metabolism, protein synthesis, and bile acid synthesis. It is expected that safe drugs can be developed by creating liver organoids that mimic the liver and studying drug-induced liver damage. Furthermore, by creating liver organoids from the iPS cells of patients with liver disease, it may be possible to provide customized treatments that allow the selection of the most suitable therapeutic drug for each patient.
Although there are challenges to be overcome in order to make this a reality, such as the need to scale up organoids and the high cost of culturing them, it is expected that this will become a tool that will greatly advance medical care.
Journal name: nature
Kidney Organoids
The kidney has the advanced function of filtering blood and excreting waste products as urine. Reproducing this filtering function that only the kidney possesses is a major expected role of kidney organoids. Although some challenges include the complex structure of the nephron, the functional unit of the kidney, and the difficulty of reproducing the reabsorption or secretion of useful substances such as glucose, organoid models of various kidney diseases, such as polycystic kidney disease and chronic kidney disease, have been developed and are contributing to elucidating disease mechanisms and developing new therapeutic drugs.
Journal name: Cell Stem Cell
1-3) Creation of organoids
Organoids are made from pluripotent stem cells such as iPS cells and ES cells. Therefore, to create organoids, pluripotent stem cells are cultured, and depending on the composition of the culture medium, the pluripotent stem cells can be divided into a collection of cells with similar properties to the "endoderm," "ectoderm," and "mesoderm."
The endoderm, ectoderm, and mesoderm are three germ layers that form early in embryonic development and differentiate into different types of tissues and organs. Organoids derived from these germ layers have distinct properties that reflect the characteristics of each germ layer.
Endoderm: Digestive system organoids such as stomach, intestine, liver, and pancreas
Ectoderm: Nervous system organoids such as brain, spinal cord, and retina, skin organoids, etc.
Mesoderm: cardiac organoids, muscle organoids, bone organoids, etc.
Culture medium | Organoids created | Features | |
Endoderm | Akvitin A, etc. | Intestinal, pancreatic, and liver organoids | Has digestive and secretory functions |
Ectoderm | Noggin et al. | Brain, skin, and neural organoids | Has neurological and sensory functions |
Mesoderm | BMP4, etc. | Bone, muscle, and cardiac organoids | Contractile function, supportive function, blood production |
From here, cells that have been induced to differentiate into endoderm, ectoderm, and mesoderm are cultured in 3D to create organoids. The 3D culture method differs for each organ, and it is a very complicated process, so even now in 2024, there is still much discussion.
2. About the organoid culture system
2-1) Differences from cell culture
Unlike cell culture, the organoid culture system accumulates stem cells or tissue-derived cells into a 3D structure and cultures structures that mimic miniature organs. Multiple cell types interact with each other to reproduce the functions of tissues, allowing for culture in conditions closer to the actual living environment.
The culture substrate also differs. Whereas single cell culture is performed on the surface of a culture dish, organoid culture often uses a three-dimensional gel-like substance such as Matrigel. Since cells grow three-dimensionally by culturing in a gel, the selection of the culture substrate is also an important culture condition.
structure | Cell type | Research Objective | Culture Substrate | Similarities with living organisms | |
cell | 2D | single | Cell proliferation and function analysis | Culture dish surface, etc. | low |
Organoids | 3D | multiple | Disease models, drug screening | Matrigel etc. | expensive |
2-2) Perfusion culture of organoids
One of the culture methods that is considered suitable for organoids is "perfusion culture." Perfusion culture is a method in which culture is performed while flowing medium , but instead of culturing without changing the medium as in static culture, fresh medium is continuously supplied, allowing organoids to be cultured in an environment closer to that of the living body.
In addition, flowing the culture medium creates pressure in the flow, which generates mechanical stress . Mechanical stress is also constantly at work in our bodies, so it is thought to be one of the important factors in mimicking the inside of the body when culturing.
Tokai Hit Co., Ltd. develops perfusion devices that reproduce constant flow, constant pressure, and pulsatile flow. We are also good at proposing solutions for perfusion culture, so if you are interested, please see the details below.
2-3) Challenges and prospects for organoid culture
Organoid culture is expected to play a major role in the development of regenerative medicine, but there are still many issues to be addressed. First of all, it is still not possible to reproduce the functions of organs. Actual organs have various functions according to their respective roles, but it is said that their functionality is still insufficient to replace real organs. In addition, it is difficult to achieve long-term and stable culture, and there are also ethical issues.
On the other hand, in order to overcome these challenges, research is accelerating, including the development of standardized protocols and the application of microfluidic devices. As the regenerative medicine market is expected to grow rapidly, it will be interesting to see how organoids will play a role.
3. Summary
This time, we focused on organoids and their culture systems.
To summarize the contents of the article, the following is true:
Organoids, often described as miniature organs, are tissues grown in vitro in three dimensions using stem cells.
There are many types of organoids that mimic different organs, and each is cultivated using a different process.
Although there are currently challenges with organoid culture, such as reproducing functionality and ethical issues, research is progressing at an accelerating pace, and great expectations are being placed on the future of regenerative medicine.
Tokai Hit Co., Ltd. develops applications that can be introduced into research in the field of regenerative medicine, including organoid culture. Tokai Hit is also good at solving solutions for researchers, so if you are interested, please click the button below for more details.
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