Growing Organs: Stem Cells, Organoids, and 3D Bioprinting.

Find out how scientists are attempting to make human organs from stem cells. While functional human organs can't be grown in the lab yet, mini-organs from stem cells can. The use of mini-organs to study organ development could lead to advances for lab-grown organs. Combined with advances in 3D bioprinting, the ability to grow organs in the lab is closer than ever. Watch the YouTube video or read on below to find out more.

Growing organs in the lab to replace failing ones is a challenging goal. Unfortunately, it's not something that scientists can do right now. But advancements are being made that could one day make this possible.

The biggest issue for organ transplantation is organ rejection. Organ rejection is when the immune system recognises the new organ as foreign. The immune system then starts to kill the cells. Much like it would during an infection. To prevent this, patients need to take drugs to suppress their immune system. A suppressed immune system leaves them vulnerable to infection and cancer. Even with these drugs, the average life of a transplanted organ is 12 years. So some patients will need many transplants in their lifetime. But if a new organ could be grown from the patient's cells. There would be no need for immune-suppressing drugs, and the organ should last them a lifetime.

Scientists are working on growing organs from adult cells. To do this, they are studying how organs develop. Organs develop from pluripotent stem cells in the embryo, called embryonic stem cells. These cells can differentiate into any cell type in the human body. As the embryo grows into a foetus, these cells multiply. They differentiate and organise themselves into mature organs. Scientists can mimic this process of organ development in the lab. Embryonic stem cells are grown in the presence of growth factors that coax them into organ-like structures. These mini-organs, or organoids, are made in a 3D culture system where they can grow in 3 dimensions. They grow within an extracellular matrix gel, like the one found outside cells in the body. Due to ethical issues with human embryos in research, there are international restrictions on funding and research. This lead researchers to try to find alternative stem cell sources.

It is was known that some organs like the intestines could regenerate their lining within weeks. Scientists also thought that adult stem cells were the source of this ability. Once they had markers to identify stem cells, they located these stem cells in the intestinal crypt base. The stem cells were isolated and grown with specific growth factors and also developed into organoids. These organoids had the same cell types and structures as the lining of the intestine. Note that Adult Stem Cells are already committed to becoming intestinal lining cells. So they can only make intestinal organoids and not other organoids like kidney or heart.

At the same time, there was another scientific breakthrough. Adult skin cells cultured with suitable growth factors could become Pluripotent Stem Cells. So instead of needing a biopsy from a specific organ. A fibroblast from a skin biopsy, which is easy to access, can be used to make organoids of any organ type. Using induced pluripotent stem cells (iPSC) instead also overcomes the ethical issues of using human embryonic stem cells.

Organoids are small. They can only grow to around 1 millimeter in size. They cannot become larger because they rely on nutrients diffusing to their centre. Diffusion can only occur across a small distance. In contrast, organs have blood vessels that supply nutrients deep into the tissues. To make functional organs, they need to grow big enough, and for this, they need to have blood vessels. But advances are being made. Although still only mm in size, a heart organoid can be grown that resembles a foetal heart. It has all the major cardiac cell types, small heart chambers, and a vascular network. After several days of culture, they even start to beat.

Organoids are advancing many other areas of science. These include drug testing, cancer research, infectious disease, developmental biology, and regenerative medicine. For example, several research groups have used brain organoids to study COVID-19. They have shown that SARS-CoV-2 (the virus that causes COVID-19) can infect and kill brain cells. This finding could explain some of the neurological effects of COVID-19, such as loss of smell and brain fog. Organoids give researchers access to human organs that are otherwise inaccessible. They also reflect human biology better than animal models.

Researchers are also trying to create tissues and organs is with 3D bioprinting. A 3D bioprinter works much in the same way as a standard 3D printer. Except that Bioink, made from living cells or organoids, is used instead of plastic resin. Cells and organoids are often printed into an extracellular matrix gel, which provides support. So far, researchers have 3D printed live tissues that are several mm thick. These tissues were also complete with blood vessels to deliver nutrients.

For example to 3D bioprinting heart tissue requires cardiac cells and blood vessel cells. Each printer nozzle is loaded with a different cell type in a nutrient gel. These cells then get printed in layers in a support gel, where the blood vessels exactly match those of the patient. The goal is to restore heart function by transplanting these tissues. Scientists have used this method to repair tissues in mice, but it has yet to be tested in patients.

While scientists can't grow functional human organs yet, insights from the study of organoids and organ development will help close the gap. 3D bioprinting can help to make thicker tissues. As well as automate the process of organoid culture. So it'll be interesting to see how iPSC, organoids, and 3D bioprinting will be used in the future. Repairing organs with organoids or 3D bioprinted tissues could be closer than ever!