Celebrating tiny organs for World Organoid Research Day 2023

Written by FRAME Volunteer Harriet Giddings

Today, 22 March 2023, is World Organoid Research Day (WORD), where researchers from all across the globe will be gathering both in-person and online to discuss all things organoid. You will most likely have heard of an organ, but what exactly is an organoid and what are they used for?

Can we grow an organ in the laboratory?

Maybe! Although we are still far from developing fully functioning human organs from scratch, an organoid may be an ideal alternative.

An organoid (or spheroid) is a fancy word to describe a cluster of cells, which can be artificially grown in the laboratory to simulate an organ. They initially originate from stem cells harvested from consenting patients during a medical procedure which are then passed on to a research laboratory. The stem cells can then be used directly in experiments or stored in a freezer for later use. Stem cells usually freeze pretty well and can survive for years in cold temperatures of up to -196°C. Organoids can then be happily grown from the frozen cells, which is an advantage for researchers who cannot access human samples.

Stem cells are the foundations of an organoid, as they are a type of cell capable of turning into other cell types when given the correct combination of molecules, growth factors and proteins. With the right food and a warm space to thrive, these tiny stem cells will bloom into small, spherical organ-like entities.

Organoids are an ideal alternative to both animal models and simple, single cell type models previously used by researchers. This is because they provide all of the cell types found within the original tissue, are three dimensional in structure and their architecture and cellular arrangement is similar to that of an actual organ.

Over the past decade, organoid research has rapidly gained popularity. In 2021, the global market size for organoid and spheroid research was valued at approximately $516.6 million USD and is expected to reach $1.2 billion by 2031 – an increase of 8.5% (1).

An accidental discovery

You may be surprised to read that discovery of the first ever organoid was actually by accident. In 2008, Dutch molecular geneticist Hans Clevers and his team attempted to harvest stem cells from intestinal biopsy tissue. He expected the cells to multiply, generating large numbers of stem cells in a petri dish for further experiments, but instead he saw epithelial-like structures forming which he nicknamed ‘mini guts’. Hans soon realised that in addition to stem cells, other cell types found in the intestine also began to form (2).

Since then, other researchers followed in Hans’s footsteps and different organoid types began to emerge. These are now used in many different research areas, including cancer, microbiology, and biomaterial science. Some of the earlier organoids were derived from the intestines, stomach, and even colorectal cancer tissue, paving the way for enhanced stem cell and cell biology research. In recent years, bone, brain and even taste bud organoids have been developed! A relatively recent organoid discovery in November 2022 was by Dr Abdullah Khan at the University of Birmingham. Dr Khan and his group published a study showing that cells in bone marrow organoids resemble and behave like real bone marrow cells. His study demonstrated that researchers have formed ‘bone marrows in a dish’ which could contribute to bone marrow cancer treatment in the future (3). Organoid research is exciting, novel and has so many advantages. It really is becoming apparent that organoids can be made to resemble just about any organ!

A variety of applications

Organoids are an ideal option for researchers who do not want to experiment on animals and want to recreate living parts of the body. There are a variety of applications for organoid research, including testing responses to drugs, investigating responses to pathogens, and even editing genes within the cells and observing functional changes. In fact, organoids can be generated from both healthy and diseased tissue, such as cancer. Tumour samples have successfully been grown into patient-derived tumour organoids, also known as tumoroids. Tumoroids have advanced cancer research in recent years, as they are used by researchers to model a tumour in the laboratory. These small cancer models may be used to study a range of complex cellular changes and responses to drugs, such as chemotherapy or anti-cancer drugs (4)(5).

An animal-free PhD

I personally think that organoids are fascinating, although I may be biased as I work with them every day. My PhD, funded by the Medical Research Council aims to identify the role of chronic stomach bacterium, Helicobacter pylori in the development of gastric cancer. To do this, I use patient-derived healthy gastric organoids to model the stomach lining and its response to bacterial infection. Over the past twenty years, most H. pylori research was carried out using mouse, or single cell-based models. Neither of these options are ideal, as H. pylori infection generally only occurs in humans and one type of cell in a petri dish doesn’t accurately represent the human stomach. By using organoids, I can explore how all of the different stomach cells respond to H. pylori and what damage is being done, which is likely a similar scenario to what is happening in a real, living stomach.

Although organoids are tricky to work with and do not always behave, the feeling you get when your experiment works is amazing and feels really rewarding. It excites me knowing that my research is as close to working on a living stomach I can get, without having to harm an animal in the process. I really believe that organoids will be the future of animal-free research – they are already gaining popularity, and more and more different organoid types are being developed every day.

Pictured above (with permission from Harriet Giddings) are healthy, patient-derived gastric (stomach) organoids grown from cells harvested from a pinch biopsy from a patient at the Queen Elizabeth Hospital, Birmingham.

These organoids are about 9 days old and started from single cells.

It is difficult to count how many cells are in each individual organoid as they vary in size. However, each organoid is composed of thousands of different cell types which originated as a stem cell. These cells release digestive enzymes, acid, hormones, or mucus.