Professor Peter Andrews
Professor of Biomedical Science and co-director of the Centre for Stem Cell Biology at the University of Sheffield.
Professor Peter Andrews is an MRC-funded scientist who coordinates the International Stem Cell Initiative, while in the laboratory his research focuses on the science that underpins stem cell therapies.
Professor Peter Andrews remembers a time when regenerative medicine was far from the thoughts of researchers working with embryonic stem cells.
“All of that early work was investigator-led, curiosity-driven research … it was really driven by an interest in the behaviour of these cells. No one had any thoughts of regenerative medicine back in those days,” he says.
Researchers were initially interested in human embryonic carcinoma cells — the malignant counterparts of human embryonic stem cells (hESCs) — and later mouse embryonic stem cells because their ability to become any type of cell in the body meant they were good for modelling development.
But when Professor Jamie Thomson, a colleague of Peter’s from his time spent at the Wistar Institute in Philadelphia, derived the first hESCs, the idea of using them to produce cells for therapeutic purposes was born. Jamie sent a batch to Peter at the University of Sheffield, and his team was the first to grow hESCs in the UK in 1999.
Since then, Peter and his co-director, the reproductive biologist Professor Harry Moore, have derived eight hESC lines of their own and deposited them in the UK Stem Cell Bank, which was established by the MRC and BBSRC in 2003. Harry has “a fair number more in the works”, says Peter, and is being funded by the MRC to derive clinical grade cells — those that have been grown in a defined set of conditions.
Pfizer now owns six of these lines, says Peter, and the company is working with Professor Pete Coffey at the UCL Institute of Ophthalmology to develop a hESC-based treatment for age-related blindness using a clinical grade version of one of Peter and Harry’s first lines, ‘Sheff-1’.
The fundamentals
hESCs can become any type of cell, and using them for therapeutic purposes will require reliable ways of differentiating them into neurons or heart cells, for example, in sufficient quantities to treat thousands, if not hundreds of thousands of patients. To do this, scientists need to know how the cells grow and differentiate, as well as how they might change when grown in the laboratory.
“Essentially a stem cell can do one of three things: it can divide and make another stem cell, it can differentiate or it can drop dead. We’re interested in trying to work out how they make decisions between those three fates,” says Peter.
Much of Peter’s work focuses on looking at the genetic changes that can occur in hESCs over time and the impact that these changes might have on this ‘decision-making’.
He has found that hESCs may over time acquire extra copies of particular chromosomes, notably 12, 17 and 20, when cultured in the lab. What’s more, these cells seem to grow better than those without the extra chromosomes. Determining whether this might make the cells more prone to becoming cancerous, or how these genetic changes impact differentiation will be important for the future of hESC therapies.
An international effort
Peter is taking an international approach to tackling this basic research. He leads on the International Stem Cell Initiative, a group of researchers from around the world that carries out projects under the auspices of the International Stem Cell Forum, a group of stem cell research funders which includes the MRC.
The first project compared many of the hESC lines held in labs and banks around the world and laid down some basic criteria for characterising the cells. The second, finished recently, compared the genomes of young and old cells to see what happens to their DNA over time.
A third planned project aims to develop a standardised test to determine what kinds of specialised cells particular hESCs are capable of differentiating into. hESCs are presumed to be able to differentiate into any kind of cell but “anecdotally, a lot appear to behave differently in terms of how they differentiate — they’re not all quite the same,” says Peter.
Expanding a cottage industry
Peter is cautiously optimistic about the field of hESC research and its ability to delivery effective therapies. Monoclonal antibodies have only begun to have therapeutic impact in the past few years, he says, more than 30 years after they were first made.
“We’re only 13 years after the first derived hESCs. The potential’s there, it’s just we have to understand how to control and work with these cells,” he says.
One major issue will be scaling up, he says. “It’s not too difficult to take some human ES cells in the lab and make them make a cell of interest, retinal cells for example, on a small cottage industry scale and do a clinical trial in 10 patients. But how do you then roll this out for 10,000 or 100,000 or a million patients? It will take time and people have to understand that.”
Find out more about the MRC and regenerative medicine.
Published April 2012