Cohesion, collaboration and clinical impact are
the watchwords of a new phase of stem cell research in Cambridge, UK
Monday, 24 October 2011
Few
areas of research have been surrounded by such hope – and such hype – as stem
cell biology. With their unique capacity to renew themselves and to give rise
to the body’s many different cell types, stem cells have the potential to
repair tissues damaged by disease or trauma: from a failing heart to lost nerve
cells.
 |
Rosettes of human, patient-specific
neural stem cells. Credit: Rick Livesey
and Yichen Shi.
|
But the
route from the laboratory to the clinic is a long one. Before patients can be
treated, many years of fundamental research and clinical testing have to take
place.
“Rushing into the clinic without basic understanding may create some
headlines but no real benefit for patients,” said Professor Austin
Smith, Director of Cambridge’s
Wellcome Trust (WT) Centre for Stem Cell Research.
“Cambridge is one of the few places in the
world that has a critical mass in both basic stem cell science and medical
translation.”
Since
2007, the University has invested over £38 million in laboratories and posts,
and has prioritised stem cell biology as a Strategic Research Initiative. There
are now 26 stem cell laboratories across the University, which have attracted
some £95 million in funding. Many of the researchers are hosted by the WT
Centre and the University’s Medical
Research Council (MRC) Laboratory for Regenerative Medicine (established by
Professor Roger
Pedersen), which focus on fundamental and translational stem cell research,
respectively.
Now, a
major effort is under way to draw together stem cell research across the
University into a new Stem Cell Institute (SCI). The SCI currently spans
several sites but the intention is to bring all these groups together
ultimately in a major new research institute on the Cambridge Biomedical
Campus. Unification will create the ideal stage for the translation of
fundamental research into clinical benefits – research such as the long-running
programme led by Professor Robin Franklin in the Department of Veterinary
Medicine, whose work on multiple sclerosis is about to move into clinical
trials (see below).
“Collaboration has always happened in
Cambridge,” explained
Professor Smith, “but pulling people
together will capitalise fully on the rich opportunities. SCI will provide a
unified organisation and a strategic direction for stem cell research that
starts from basic science but sets clinical delivery and interaction with bio
industry firmly in its sights.”
A key
component will be interdisciplinary research teams that link stem cell biology
with molecular disease mechanisms through to clinical applications.
Alongside
Professor Smith in spearheading the reshaping will be the newly established
Chair of Stem Cell Medicine, to which Professor Oliver Brüstle has been
elected. Professor Brüstle is currently Director of the Institute of
Reconstructive Neurobiology at the University Of Bonn, Germany, and an expert
in stem cells of the nervous system and their application in neurodegenerative
disease.
Professor
Brüstle – who notably fought for legalisation of research on human embryonic
stem (ES) cells in Germany and finally became the first scientist to obtain a
respective license – regards stem cell therapies as “just another way to treat disease”. He is at pains to emphasise
that cell transplantation is not the only way that stem cells can bring
clinical benefit.
“In fact, a much closer prospect is the use of
stem cells to study specific diseases in the laboratory and to develop new
drugs.”
Another
important opportunity is the possibility of improving cancer treatment by
identifying and targeting tumour stem cells.
“Of course there are challenges to overcome
before stem-cell-based medicine is commonplace,” added Professor Brüstle.
“For example, we need to learn more about how
human ES cells differ from mouse ES cells, and how their fate is controlled.”
In
fact, a major discovery about the differences between human and mouse ES cells
was made in Cambridge. Professor Pedersen and Dr Ludovic
Vallier and colleagues showed that human ES cells represent a
developmentally more mature stage than naive mouse ES cells. This can explain
why some procedures for producing specific cell types from mouse ES cells do
not work well with human cells.
“Human ES cells are less versatile. This
research has changed the way stem cell researchers think about human ES cells,” explained Professor Smith.
The
goal now is to understand this difference at a molecular level. Professor Azim Surani at the WT/Cancer
Research UK Gurdon Institute in Cambridge has pioneered a deep-sequencing
technique to do precisely this. His team can now analyse the entire
transcriptome (all the gene products) in a single stem cell, opening the door
not only to understanding the specific nature of human ES cells but perhaps
also to how to make them more like mouse cells.
Professor
Smith foresees a time when stem cells will permeate all areas of biology.
“Stem cells are going to be instrumental in
taking us to the next level of understanding about how cells make decisions
about their fate. Increasingly, we’ll see them being used in laboratories as
systems to look at basic biological questions that may have nothing directly to
do with stem cell biology. Stem cells will soon become the research tool of
choice in mammalian cell biology.”
Self-service
brain repair in multiple sclerosis (MS)
Researchers
led by Professor Robin Franklin at the MS Society Cambridge Centre for Myelin
Repair recently discovered a molecule that is capable of activating the brain’s
own stem cells to repair damage caused by MS. Now, preparations have begun for
a small-scale trial to test whether this process can regenerate lost nerve
function, for which there is currently no treatment available.
Nerve
fibres are progressively damaged in MS because they lose a protective coating
of myelin when the cells that make it (the oligodendrocytes) are destroyed by
the body’s immune system. The aim of the new treatment will be to stimulate
stem cells that occur naturally in the brain and which have the ability to
regenerate lost oligodendrocytes.
In the
course of over two decades of research, Professor Franklin and colleagues have
found that one of the major problems in MS is that the patient’s stem cells
lose the ability to become normal oligodendrocytes. When oligodendrocytes are
destroyed during the MS disease process, they are not replenished from the
brain’s pool of stem cells. But the ability can be regained when the patient’s
stem cells are activated through the retinoid acid receptor RXR-γ, as shown in
collaboration with colleagues in Edinburgh using animal models and published in
Nature Neuroscience in January 2011.
The
discovery was a landmark moment in the search for treatments for MS, as
Professor Franklin explained.
“If we can encourage the patient’s own stem
cells to develop into oligodendrocytes and replace the lost myelin, then this
might restore the nerve functions lost in MS.”
The
idea behind the proposed treatment is not only to repair the damage but also to
arrest any further damage caused by the patient’s immune system. An effective
treatment for halting the destruction of oligodendrocytes, alemtuzumab
(Campath), was developed in Cambridge by Professor Alastair Compston and Dr
Alasdair Coles at the Department of Clinical Neuroscience.
The
prospective new trial, which is currently being designed by Dr Coles together
with colleagues at University College London and the University of Edinburgh,
and is not yet recruiting patients, plans to use a licensed drug, bexarotene,
which activates RXR-γ.
Professor
Franklin added: “Essentially, the
philosophy of our approach is not to transplant stem cells from elsewhere but
to encourage the patient’s own stem cells to do the work of repairing the
damaged tissue.”
Source: Cambridge
University
.........
For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/
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