Topic Review: Stem Cells

200,000 Number of blood-creating stem cells found in bone marrow

3,000 Number of clinical trials registered using adult stem cells

$9,600,000,000 Global market for stem cell therapies in 2019

5659 Number of Stem cell startups and companies on Angelist

159,255 Number of scientific publications on PubMed with stem cells as a major theme

 

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ORIGIN STORY

How these miraculous cells were discovered?

Life begins from a single cell, the fertilised egg. The changes that this single stem cell goes through to become an adult animal is called embryonic development. Embryonic development has been studied for hundreds of years, so scientists have been aware of the concept of stem cells for some time. However, physically collecting stem cells and controlling what they turn into wasn’t achieved until much later.

In the 1950s, studies of bone marrow identified stem cells which could give rise to all the different blood cells. These stem cells are called ‘adult stem cells’ – rare cells that replace certain parts of the body. Later it was found that adult stem cells exist not only in bone marrow but in other locations, like the gut wall to replace intestinal cells. Whilst these discoveries opened up new exciting possibilities, adult stem cells can only turn into a certain cell types.

It was not until 1981 that the initial theories from embryonic studies were experimentally confirmed. Martin Evans from Cardiff University was the first person to collect mouse embryonic stem cells and study them in the laboratory. It took another 17 years for James Thomson from Wisconsin-Madison University to do the same with human cells. What followed was an enormous ethical storm. By collecting cells from embryos, scientists had opened a Pandora’s box of ethical issues. Embryonic stem cell research was heavily restricted in multiple countries and banned in others.

Unlike adult stem cells, stem cells from embryos are able to transform into all 200+ cell types of the body. Studying them allowed scientists to pinpoint stem cell specific molecular pathways. The amalgamation of this research was the discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006. Yamakana was able to ‘turn back the biological clock’ and make mouse skin cells return to their embryonic stem cell like state.

The discovery of iPSCs revolutionised the field of stem cells. No longer constrained by difficult stem cell donations and ethical issues, stem cells are now routinely used around the world for research such as modelling diseases and testing out new medicines in the lab. As well as their amazing research potential, stem cells have the ability to replace damaged tissues in the human body, offering a whole new way of treating diseases called ‘regenerative medicine’.

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BACKGROUND

Are any stem cell therapies effective?

100% Affirmative via 5 experts

Read the full answers to this question here. The large amount of hype surrounding stem cell research in the media suggests that they hold great clinical potential, but do any therapies that use stem cells actually work?

Identifying which stem cell therapies are effective and safe is becoming increasingly difficult due to the complexity of this field of medicine. Stem cells themselves are not all the same. The adult human body has small populations of limited-potential stem cells which are essential to replenish certain parts of the body, for example to heal cuts. These stem cells are different from embryonic stem cells, which are found in very early embryos and can turn into all 200+ cell types of the body. Yet another group of stem cells, iPSCs, are made entirely artificially from normal cells in the lab. These three different sources of stem cells, coupled with their diversity of application, makes the field of stem cells a difficult one to navigate.

Despite the complexities, our experts have unanimously confirmed that there are some stem cell therapies that have been proven effective. “Some effective, clinically approved stem cell therapies have existed for some time” writes Phillipa Harding from University College London. “Transfer of stem cells from healthy donors to treat blood disorders such as sickle cell anaemia and cancers are well established, and have proved lifesaving for many patients with these diseases where alternative treatment options are limited, or non-existent”.

Apart from these therapies that we know are effective and are being routinely used, another generation of stem cell therapies are currently being investigated. These use the highly-amenable iPSC variety of stem cells, as opposed to more traditional ‘adult’ stem cells.

“Such therapies are still in their infancy but are beginning to bear fruit ” explains Dr Barney Bryson from University College London. “Like transplantation of iPSC-derived retinal pigmented epithelial (RPE) cells, which has shown promise as a treatment for age-related macular degeneration, as well as intraspinal transplant of embryonic-derived neural precursor cells as a potential therapy for amyotrophic lateral sclerosis (ALS). With recent advances in regenerative medicine, it is very likely that this type of therapy will become far more widely employed and that the range of treatable diseases will greatly increase.”

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THE CONSENSUS

Are stem cell therapies safe?

100% Affirmative via 5 experts

Read the full answers to this question here. There are numerous news stories which describe desperate patients seeking out experimental stem cell therapies with devastating consequences. These accounts make many people wonder, are stem cell therapies safe?

Dr Karl Willert from the University of California answers: “Absolutely. Having said that, this only applies to stem cell treatments that have been properly vetted and, most importantly, have gone through clinical trials and have received FDA approval.” To date, stem cell therapies that have received FDA approval (i.e. are licensed for use in the USA) are for the treatment of blood disorders. In Europe, stem cell therapies have also been approved for other uses such as eye burns.

Whilst experts are in agreement that the approved therapies are safe, it is too early to say the same for therapies that are still in experimental phases. Whilst research is generally promising for these newer therapies, they are not yet ready to be used and so it is a major concern when they are offered in private clinics, often for extortionate prices. “sadly, many crooks have started offering all kinds of “stem cell therapies” that could be very dangerous and lead to the development of tumors and other problems.” says Dr Michael Telias from the University of California.

This distinction between medical interventions that have and have not been approved is important not only for therapies with stem cells, but any medications. On the whole, approval is only granted when there is overwhelming evidence that the intervention is safe.

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THE CONSENSUS

Are some diseases better suited for stem cell therapy?

100% Affirmative – 8 experts

Read the full answers to this question here. The unique selling point of stem cells is that they can become any type of cell that we require. Whilst this opens many exciting possibilities, does it mean that stem cells are the answer to every disease, or are some diseases better suited for stem cell therapy than others?

So far, it seems we can use stem cells clinically in two different ways according to experts. The first uses stem cells to replace parts of the body that have become damaged. This is what happens in the clinically approved blood stem cell therapies. Blood-based diseases are well suited to such a therapy as cells are accessible and blood cells are naturally replenished by stem cells that persist throughout life.

It is also possible to use transplants to replace tissues that don’t have stem cells writes Professor Carolyn Carr from Oxford University: “Pancreatic beta-cells which make insulin can be formed from stem cells in the lab and it is hoped will be able to be used in the treatment of type 1 diabetes by transplanting new beta cells in diabetic patients” . This approach could offer an alternative to tissue or organ transplants, which are often limited by available donors.

An alternative use of stem cells is to implant them into damaged tissue and let them stimulate the patient’s own cells to heal. For example, “injecting stem cells into the heart has been shown to be beneficial by damping down the inflammatory reaction and inducing the formation of new blood vessels” explains Professor Carr. Another more recent example is that stem cells have been used “to treat Covid-19-induced pneumonia, where its anti-inflammatory effects can weaken the associated ‘cytokine storm’ ” writes Abigail Isaacson from King’s College London.

Dr Karl Willert from the University of California summarises: “I would say any condition where tissues, organs or body parts are damaged, diseased or dead will potentially benefit from stem cell treatments.”

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THE CONSENSUS

Can stem cells be grown into organs in the lab?

60% Affirmative – 5 experts

Read the full answers to this question here. Stem cells can turn into any type of cell, so an obvious goal would be to grow whole organs in the lab in order to transplant them into humans or use them as an alternative to animals to test new medicines. But, is it actually possible to grow organs?

As of yet, no one has been able to grow an entire functioning organ in the lab writes Dr Bryson from UCL: “It is likely that this will be possible in the medium-term future but this will very much depend on the type of organ. For relatively simple organs, consisting largely of a single cell type (such as hepatocytes that make up the liver), this should be achievable.” More complex organs pose additional challenges to scientists, such as the highly complex 3D shape of the heart.

A step towards this goal is the creation of ‘organoids’, 3D microscopic ‘mini-organs’. Organoids can mimic many of the normal functions of a range of organs and are being investigated extensively for their use in studying diseases in humans and testing new medicines. As Emily Read from King’s College London summarises, “Many researchers are trying to make organoid cultures more complex and representative of actual organs. In the future, it is possible that entire organs could be grown in the lab from stem cells, however there is further work to be done before this is a reality.”

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“Stem cells have the potential to grow into any cell type in the human body. They have already proved invaluable for studying human development, help us understanding how our bodies work, and test new treatments for diseases in the lab. Their unlimited potential for growth means they are also a useful tool for treating diseases caused by degeneration or permanent damage to cells, such as existing treatments for bone cancers through marrow transplants from donors.

Additionally, innovation in induced pluripotent stem cell (iPSC) technology, where adult skin/blood cells can be induced into stem cells and encouraged to form any cell type under precise controlled conditions, means people can have their own cells transplanted back into them, without risk of rejection. Ability to generate stem cells allows patients to receive treatment without having to wait long periods for donor tissue while their condition potentially worsens. For example, there is a huge shortage of cornea donors worldwide, but the first human iPSC cornea transplant from adult skin cells was performed in 2019.”

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TAKEAWAYS

• Stem cells can turn into any kind of specialised cell
• There are three main sources of stem cells: special adult tissues such as the bone marrow, embryos and artificially created iPSCs
• Stem cells can be used to replace damaged tissues in the body or promote healing
• Some stem cell therapies have been used to treat patients for decades
• Newer types of stem cell therapies are being developed against a whole range of different diseases. However, before they have been clinically approved they are not proven safe and so should be used without a proper understanding of the risks.