Introduction :
In this article, we are going to share some common facts and a general understanding of the organoids, the most recent research subject, that every developmental biologist is curious about. So without any pause, let's discuss the outline of the subject that you will get to know in this article series.
- A quick history about the development of organoids.
- Why do we need organoids?
- How to make organoids? (The organoid culture)
- Various applications of organoids.
- Future possibilities.
In this article, you will get the answer to the first three questions and other questions are discussed accordingly.
What are organoids?
Organoids are tiny, self-organized, three-dimensional in-vitro tissue cultures that are derived from pluripotent stem cells or stem cells. They are a miniature simplified version of an organ, which shows similar micro-anatomy. They are derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells. They can self organize in 3-D culture media with differentiation capacity.
A quick history
The quest for synthetic human organs laid the foundation stone of organoid research. Self-organization of dissociated sponge cells was the first achievement in this field. With time, scientists made it possible to generate different types of organs of amphibia and the embryonic chicks from the organ tissue in the process of dissociation and re-aggregation in-vitro. With advancements in stem cell biology, observations like tissue differentiation etc. were made with time. A shift in culture media from 2-D cell culture to 3-D cell culture allows the development of complex three-dimensional organ structures. Now organoids of the vascular liver, differentiated balls of neural cells(brain organoids) or cerebral organoids, cardiovascular organoids are cultured in different labs across the world.
(P.S. I just gave a glimpse. The whole history can be read by the Wikipedia link, which I am attaching below)
Why do we need organoids?
Let's discuss something about 2-D and 3-D cell culture.
2-D Cell culture
2-D cell culture or cell culture is the process by which cells are grown under controlled conditions, generally outside their natural environment. Typically, they grow on flat 2-dimensional dishes, therefore called 2-D cell culture.
2-D cell cultures are cheap and easy to deal with. However, due to many benefits, 3-D cell cultures are preferred nowadays. Before discussing them in detail, let's discuss 3-D cell culture.
3-D cell culture
3-D cell culture is an artificially created environment in which biological cells are permitted to grow or interact with their surroundings in all 3-dimensions. 3-D cell culture sustains cells to grow in all directions, identical to how they would in vivo.
Here is the comparison between 2-D cell culture v/s 3-D cell culture.
Cell shape
2-D cell cultures are flat, elongated and expand only in 2-dimension, whereas 3-D cell cultures retain the natural cell shape. They form 3-D aggregated spheroids with multiple layers.
Cell exposure to medium
In a 2-D medium, all cells get nutrients and growth factors uniformly, as a result, most of the cells are monotonically in the same stage of the cell cycle. However, in 3-D medium nutrients are not equally divided. Core cells remain inactive, which represents tumor cells.
Cell junction
Cell junctions are less common in 2-D culture. Cell to cell communication is hard to find. However, in 3-D cell culture, cell junctions are very common. And cell to cell communication is well illustrated.
Cell differentiation
Very poor cell differentiation is seen in 2-D cell culture. Whereas cells are well differentiated into various germ layers(if cells of the fetus are taken) in 3-D culture.
Drug sensitivity
Cultures of 2- D cells show poor drug metabolism. However, in 3-D cell culture, drugs are well metabolized and give an accurate response to drug effects.
Cell proliferation
In 2-D cell culture, cells proliferate unnaturally at a rapid pace. But in the 3-D cell, the culture proliferation rate is realistic and can be controlled.
Apoptosis
Apoptosis is the death of cells which occurs as a normal and controlled part of an organism's growth or development. It is also called natural cell death. 2-D cell culture is prone to apoptosis, whereas 3-D cell culture is highly resistant to apoptosis.
Responses to stimuli
Inaccurate responses are obtained when 2-D cell cultures experience physical stimuli. They don't experience Gravity. However, 3-D cell cultures give an accurate response to mechanical stimuli. They also experience gravity and give an exact representation of life in vivo.
Cost
Uses and analysis
2-D cell cultures are easy to handle. Experiments are easily replicable, while 3-D culture is hard to monitor and interpret data. Maybe 3-D cell cultures are highly expensive, handling them is not an easy task, but in near future, scientists will be acquainted with this new system. Here is another cause, why we need organoids. With the development of organoid technology, the use of animal models will be highly reduced, which leads to less ethical issues.
In the next article of this series, we will discuss How to make organoids.
Reference:
- https://en.m.wikipedia.org/wiki/Organoid
- https://www.sciencealert.com/scientists-used-stem-cells-to-make-mini-brains-they-grew-rudimentary-eyes?utm_campaign=skedlink&utm_medium=gallery&utm_source=skedlink
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040128/
- https://www.nature.com/articles/s41580-020-0259-3
