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Regeneration: Taking stock

by Guest Author on 13 Sep 2012

Ian Wilmut (Copyright: MRC Centre for Regenerative Medicine)

Ian Wilmut (Copyright: MRC Centre for Regenerative Medicine)

Professor Sir Ian Wilmut was formerly Director of the MRC Centre for Regenerative Medicine at the University of Edinburgh. Famously, he led the research group that first cloned a mammal from an adult body cell — Dolly the sheep — in 1996. Sarah Harrop spoke to him about how far regenerative medicine has come and what the future might hold.

What are some of the different approaches to regenerative medicine currently being undertaken by scientists?

Very broadly, there are two main approaches at the moment. We’re using stem cells to understand the mechanisms that cause some degenerative diseases so that it’s possible then to identify drugs that are able to prevent the development of symptoms. The second strategy is to produce cells that can replace those that have died or ceased to function normally in degenerative diseases.

What benefits and insights might the first approach offer?

To identify the molecular mechanisms that lead to disease it’s important to be able to study cells that are affected by the disease in the lab. A key innovation that makes this possible is our ability to treat skin cells so that they are changed and become very similar to embryo stem cells. These cells — induced pluripotent stem cells, or iPS cells — are able to form all of the different cell types and grow in culture for very long periods. This makes it possible to produce the large number of cells required for research.

We can turn these iPS cells into other cells, for example the nerve cells (neurons) that are damaged in motor neuron disease. By comparing iPS-produced neurons from a patient with equivalent cells from a healthy person, preferably a relative, it’s possible to identify the molecular differences between healthy and diseased cells that cause the disease symptoms.

The final step is to devise tests that can be carried out automatically by robots to identify compounds that are able to prevent the occurrence of the abnormal function, and therefore treat symptoms of the disease. Different groups worldwide are pursuing this approach in a search for treatments for diseases such as Parkinson’s disease, some causes of heart failure and multiple sclerosis.

How about the other strategy: producing cells to replace damaged or faulty cells?

This is very challenging because the cells to be transplanted must be very pure and of exactly the required type. It is very encouraging that clinical trials of these so-called cell therapies are now beginning — for example to treat stroke — and we can expect many more in the future.

Of course any potential therapeutics using, or based upon, cells must be tested like any new drug treatment, and this process takes several years.

How’s the UK doing in terms of stem cell research? 

We are very competitive in the UK and we have excellent support from funding bodies like the MRC, BBSRC, the Wellcome Trust and charities.

We’re also very fortunate to be working in a country with a supportive but robust legal framework for stem cell research.

We’re approaching the most expensive phase for stem cell research now, so we will need ongoing support for this to continue.

Which approaches do you think will ultimately have the most therapeutic value?

In future we’ll probably know even more about changing cells from one type to another so that it will become possible to produce exactly the type of cell that we need from a patient’s own tissue. An alternative approach is to learn how to change cells from one type to another within the body using drug-based treatments, rather than by cell therapy where cells are taken out, differentiated in the lab and then put back.

But for diseases like diabetes you’d need too great a supply of cells to be able to correct the disease, and cells would be attacked by the immune system. So instead it might be possible to transplant cells within a capsule inside the body to protect them from the immune system while allowing them to produce insulin and release it into the bloodstream as required.

Currently the only option for replacing cells [other than blood cells, where bone marrow transplantation can be used], is to use donated tissue from people who’ve passed away. There’s a shortage of supply of these tissues, so there will be a major role for lab-produced cells in transplantation in the future.

What sort of factors influence success in regenerative medicine research?

Practical considerations can play a big part. For example, if you’re carrying out research on the eye it’s easy to see what’s going on by using an ophthalmoscope and to remove the cells again if they are causing harm — but if you’re working on organs inside the body, particularly in tissue such as the brain, you wouldn’t be able to observe what was happening in the same way.

So I think that, at first, people will have to identify what seem like niche products and develop the first cell therapies that way.

How do you see the field progressing over the next 20 years?

Over the past 200 years we’ve learned how to control and treat most infectious diseases which used to kill thousands of people, many during childhood, or leave them with symptoms which affected them for the rest of their lives – such as in polio.

Today, most of these diseases are controllable. We’re now at the point where we can begin to treat the death or degeneration of cells which will have an impact on many diseases — multiple sclerosis, motor neuron disease, cardiovascular diseases. We are entering a new era. In 20 years we will have taken the first exciting steps, but it is important to recognise that it will take longer for regenerative medicine to reach maturity.

This article also appears in the Autumn 2012 edition of Network magazine.



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