SPOTLIGHT ON STEM CELLS

Stem cells: fulfilling the promise

Breakthroughs in stem cell research provide hope for patients, but it's also an optimum time for scientists in the field.

If you're interested in the science, there's probably a skill set of yours that can be used somewhere — you don't have to be a PhD-level research scientist to be involved in this field. Tenneille Ludwig, WiCell Research Institute

AT COLUMBIA University in New York, the circuitous route of postdoctorate scientist Sarindr Bhumiratana shows that there is no single career path in stem cell research. Bhumiratana initially studied chemical engineering, but flourished in biomedical engineering during a stint at Columbia's laboratory for stem cells and tissue engineering.

Bhumiratana went on to help develop a research programme to explore the use of stem cells to grow customized bones for patients whose heads and faces need to be rebuilt and for the healing of disfigurements that can leave psychological scars. He is now pushing this work towards clinical applications.

Bhumiratana's advisor at Columbia, Gordana Vunjak-Novakovic, describes him as a sterling example of how accessible stem cell research is as a career.

“This is a great demonstration of how you can use stem cells to solve difficult, complex problems, and how you can enter stem cell research in many different ways and go far,” Vunjak-Novakovic says.

Since human embryonic stem cells were first isolated in 1998, stem cell research has provided a dazzling variety of possibilities for improving patients’ lives. The multi-disciplined approaches needed to research them and the huge capacity for further discovery means the field has much potential for scientists as well.

iPS cells reprogrammed from a woman's skin. These cells can be matured into other cells of the body, and used for studying models of disease. Credit: CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE

Although some of the initial excitement around stem cells can be put down to hype, advances over the last 15 years have led many of these promises to bear fruit. Indeed, 2013 has been touted as a big year for regenerative medicine. “Now more than ever, we're on the cusp of some dramatic breakthroughs with stem cells,” says Tenneille Ludwig, director of cell banking and distribution at the WiCell Research Institute in Madison, Wisconsin.

Crucial distinctions

Most types of stem cells are specialized and can only differentiate into a certain kind of tissue — for instance, hematopoietic stem cells are the genesis of all the other blood cells.

The most valuable stem cells for research are embryonic stem (ES) cells, since they are pluripotent, capable of becoming any tissue in the body. Two clinical trials involving retinal cells derived from human ES cells for patients with Stargardt's macular dystrophy and dry age-related macular degeneration are being led by Advanced Cell Technology (ACT) in Massachusetts, and preliminary findings appear encouraging, with some vision improvements seen.

However, in recent years, breakthroughs in stem cell research have led to the development of so-called induced pluripotent stem (iPS) cells, which are typically mature cells genetically reprogrammed to become pluripotent ones using retroviruses.

This year, ACT hope to launch the first human iPS cell trial, to generate blood platelets from these stem cells. If successful, it would mean a source of blood platelets for patients requiring transfusions without the need for donors.

It may also be possible to turn adult stem cells into different types of cells entirely. For instance, scientists hope to transform pancreatic ductal cells to pancreatic islet cells that can manufacture insulin for people with diabetes, says K. Lenhard Rudolph, scientific director of the Leibniz Institute for Age Research in Jena, Germany.

Acceptable alternatives

Much of the initial resistance to stem cell research focused on stem cell lines developed in the 1990s, which originate from human embryos. The development of human iPS cells in the 2000s, which gave researchers pluripotent cells without an embryonic origin, somewhat circumvented this controversy, says Thomas Hyde, chief operating officer at the Lieber Institute for Brain Development in Baltimore. ES cell experiments are likely to remain necessary, however, as given the reprogramming they have undergone, it is still uncertain how useful or safe iPS cells are.

Nonetheless, plans for major projects in the next three to five years are poised to generate significant funding for iPS stem cell research, says Erik Forsberg, executive director at WiCell. He describes a programme “to generate tens of thousands of new human iPS cell lines from thousands of people from both the general population and patient groups.” This will allow wide-scale comparison of healthy stem cell lines against those in patients, helping to model diseases and provide insights on their biology. The projects will be broadly funded, with investment coming from the National Institutes of Health, the California Institute for Regenerative Medicine, the Allen Institute for Brain Science based in Seattle, the StemBANCC partnership managed by the University of Oxford, and the Wellcome Trust and Medical Research Council in the United Kingdom.

Options abound

The wide range of funding bodies investing in stem cell research echoes the variety of career paths in the field in addition to the scientists and physicians who conduct the research and the technicians in the lab. Companies such as Stemcell Technologies in Vancouver develop the reagents, instruments and techniques used in stem cell research, and do much of the other specialized work required, such as DNA extraction and sequencing, epigenetic profiling, and sometimes entire preclinical studies.

Gordana Vunjak-Novakovic, whose lab at Columbia University uses stem cells to develop tissue grafts, consults with a surgeon about implantations. Credit: LABORATORY FOR STEM CELLS AND TISSUE ENGINEERING COLUMBIA UNIVERSITY

Quality assurance is also essential — people who ensure labs follow good manufacturing and clinical practices and adhere to guidelines governing what might go into the human body. “You have to be passionate about getting the work done right, have a meticulous personality with a lot of attention to detail, and work with top management down to technicians and even janitors cleaning labs,” says Jessica Martin, director of quality assurance and marketing at WiCell.

There are jobs in stem cell research outside the lab as well. For instance, the regulatory framework around stem cell science creates a need for legal specialists to consider the issues. “There's also definitely a need for people who can write grant applications, for sales and marketing staff, and for those who can educate the general public on the politics and ethics of the work,” Ludwig says. “If you're interested in the science, there's probably a skill set of yours that can be used somewhere — you don't have to be a PhD-level research scientist to be involved in this field.”

Enthusiasm, however, is a must. “By now, everything that is easy to do has probably been done a long time ago. Today we're facing difficult problems, and to solve those you need excited people who never give up, who really work relentlessly toward accomplishing something,” Vunjak-Novakovic says.

Given the multi-disciplinary nature of stem cell research teams, “the ability to learn the language of other disciplines is extremely important,” adds Terry Thomas, senior vice president of research and development at Stemcell Technologies. When interviewing candidates, he asks questions outside a person's area of research, “to get a look at their ability to process new ideas, catch on quickly and to test intelligence and flexibility.”

Experience outside science is also advantageous. “I'm looking for people with broad horizons, which matters in a frontier field like stem cell research, so I really look for things on resumes like travel, volunteer work, as well as people who were heads of student associations or ran a business. People who can make things happen,” Thomas says.

Given the pace of evolution with stem cell research, Thomas says, “you will need to constantly learn and almost anticipate new developments. You need to be flexible”.

There are critics who claim that stem cell research has failed to live up to its promise, but those within the field have seen the advances. “Now is probably the best time ever to work in the field of stem cells,” Vunjak-Novakovic says.

Hyde agrees: “The promise of stem cells cannot be underestimated, but it's not simple work that can occur after just a week or a month.” That said, “ to go from initially deriving human ES cell lines to clinical trials with them in just 10 years or so is pretty impressive. It's still amazing how far we've come in so short a time.”

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