Demography: Interview

How stem cells can extend healthy old age

New therapies could regenerate old cells and transform the lives of the elderly, explains Dr. Tilo Kunath of the MRC Centre for Regenerative Medicine.
A microscope image of neural stem cells (in green) made by Dr. Tilo Kunath from human embryonic .../ Credits: Tilo Kunath
Scientists tackling chronic and degenerative diseases are growing body cells and tissues to replace or fortify damaged cells. In the last year, doctors in Sweden have transplanted artificial windpipes grown from stem cells into two throat cancer patients. Elsewhere scientists have cultivated heart muscle and liver cells and even made bone from stem cells taken from fat. As the age of stem cell medicine takes shape, researchers like Tilo Kunath are exploring how to ensure a healthier old age.

Allianz Knowledge: You are based at the Centre for Regenerative Medicine in Edinburgh, Scotland. What exactly is regenerative medicine?
Tilo Kunath: Regenerative medicine is about treating conditions and diseases that involve the loss of normal cells or tissues. It’s also about finding ways to prevent that degeneration, or ways to regenerate lost cells.

I work on neurodegeneration which happens when parts of the brain degenerate due to old age or specific diseases such as Parkinson’s disease or Alzheimer’s. Neurodegeneration isn’t strongly associated with modern living or western lifestyles, unlike obesity and some cancers. But it is associated with old age.

So regenerative medicine is concerned with how functional we are in old age. A lot of our work is going to impact hugely on the quality of life people have in their old age. It may result in a lot more members of society making contributions into their 70s and 80s.

How does regenerative medicine work?

The easiest vision for regenerative medicine is replacing lost cells by transplanting them with new cells —cell therapies. In the diabetes field, for example, there is a lot of work on transplanting cells that produce insulin.

Parkinson’s patients lose cells that produce dopamine, responsible for movement and emotions. My lab is applying for funding to create dopamine-producing neurons from human embryonic stem cells for transplantation into people with Parkinson’s, hopefully moving towards clinical trials by 2019 or 2020.

But what my lab mostly does is not cell therapy but disease modelling, another form of regenerative medicine. For example, we take skin cells from people with genetic forms of Parkinson’s and turn them into induced Pluripotent Stem Cells (iPSCs), a type of stem cell that can make any other cell.
Dr. Tilo Kunath Dr. Tilo Kunath, research fellow at the MRC Centre for Regenerative Medicine, Edinburgh: "A lot of our work is going to impact hugely on the quality of life people have in their old age. It may result in a lot more members of society making contributions into their 70s and 80s." What do you then do with these stem cells?
One thing we would not do is transplant them. These cells are destined get Parkinson’s.

What we can do is turn them into dopamine-producing neurons and investigate what makes them degenerate and die. We can’t poke around in peoples’ brains to study the disease process so we are using their stem cells instead.

This means we can start testing drugs on them. Parkinson’s, Alzheimer’s and other neurodegenerative diseases are very hard to target and having cellular models will help drug screening a lot.

Has the development of iPSCs made the ethical debate about embryonic stem cells less pivotal?

It is certainly less pivotal. Of course we don’t know which embryo is going to get Parkinson’s so we wouldn’t use embryonic stem cells for this work. However, we can identify people with genetic forms of Parkinson’s and request a skin biopsy, which we can convert to iPSCs and to neurons. This is perfect for disease modelling.

The ethical issues have not gone but the fact that there is an alternative now means that a lot of labs, for example in Ireland, can get going. On the other hand, the big advantage of embryonic stem cells is that they have been around a long time and people know how to work with them. It would be difficult, time-consuming and costly for many labs to completely switch to new iPSCs.

What drugs or treatments have developed directly from stem cell research?
Macular degeneration [a major cause of blindness in old age] is probably the low-hanging fruit for cell replacement therapy and has already started.

But the big problem is that any transplantation therapy is going to be very expensive and only suitable for a small number of people. The financial gain is not going to be large so the idea that big pharmaceutical companies will latch onto it doesn’t look very hopeful.

However, big pharma are very interested in using iPSCs for screening drugs, as a new Parkinson’s or Alzhemier’s drug could be sold to millions.
The Centre recently announced that it is growing bones using fat cells. How is this possible?
That is Prof Bruno Péault’s lab. There is a type of stem cell called a pericyte you can get from fat and other tissues which, when grown in the lab, can turn into things like bone. These could be used for bone grafts and other purposes.

This leads on to another aspect of cell therapy, which is also being used to treat liver diseases — transplanting cells that don’t directly replace the cells lost but make the environment better for cells to repair themselves. They act like a repair catalyst.

So there are stem cells used to replace lost tissues, stem cells used for disease modelling, and now stem cells used for their ability to help other cells regenerate.

How far advanced is this field? When will it be mainstream medicine?

We can see massive progress in the understanding of how these diseases develop. There are a lot of regenerative medicine centres springing up around the world.

What should follow is the ability to manipulate, prevent or alter the course of these diseases. I am working with chemists to try and alter the behaviour of a protein underlying Parkinson’s disease. If we can stop these proteins misbehaving we can potentially stop these diseases in their tracks or even prevent them from developing.

And if we also understand the genetic probability of getting a particular disease and identify the people at risk, we could offer them these new preventative therapies that would prevent them from getting it.

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