Everything in an adult organism comes from stem cells. As scientists learn to better understand and direct the path of these cells, it will enhance basic biological and clinical research. The experts interviewed here see a long future ahead for researchers in these areas.
Genome Institute of Singapore http://www.gis.a-star.edu.sg
Lund University http://www.lu.se/o.o.i.s/450
Massachusetts Institute of Technology http://web.mit.edu
Newcastle University http://www.newcastle.ac.uk
University of Cambridge http://www.cam.ac.uk
University of Washington http://www.washington.edu
WiCell Research Institute http://www.wicell.org
With all of the excitement during the past few years, stem cells seem like an entirely new realm of biology and medicine. Nonetheless, scientists started studying these cells long ago. Now, though, scientists seem on the verge of turning stem cells into one of science’s most powerful tools of all time. In fact, these cells help scientists learn more about basic biology and give physicians new tools against disease. The real power of these cells lies ahead, and there will be plenty of room for trained scientists.
“Embryonic stem cells are a cellular window into pluripotency and infinite replicative potential,” says Edison Liu, executive director at the Genome Institute of Singapore. “So the detailed investigation on stem cells will give insight into fate decisions of early embryonic cells.” He adds that these cells offer great potential as regenerative therapies.
“It doesn’t get mentioned so much,” says Beth Donley, executive director of the WiCell Research Institute at the University of Wisconsin, Madison, “but stem cells provide an incredible opportunity to study developmental biology.” For these cells, the breadth of application will depend largely on the extent of the scientific imagination. Austin Smith, chair of the Institute for Stem Cell Biology at the University of Cambridge, says, “Stem cells are used in many different types of research: uncovering basic developmental mechanisms, exploring mechanisms of cell proliferation, and trying to develop cell transplantations and drug screening platforms.” He adds, “For me, it’s just curiosity driven. I want to understand how these cells work and what they do.”
Spreading Stem Cells Around
With stem cells, most people think of using them for cell therapy or regenerative medicine in general. For example, James L. Sherley, associate professor of biological engineering at the Massachusetts Institute of Technology, says, “You could expand adult stem cells, which have long-term division capabilities, and then induce them to make non-stem cell progeny cells that differentiate into mature cell types, which could be used directly or used to make therapeutic biomolecules.”
Stem cells could also improve gene therapy. A hematopoetic stem cell, for instance, could be engineered to carry the desired gene. Then, the hematopoetic cells could be put in a person through a bone marrow transplant. The person’s body would then grow mature cells that express the gene - one that cures a disease.
Sometimes, scientists can even gather stem cells from unexpected sources, such as umbilical cord blood. Colin McGuckin, professor of regenerative medicine at NewcastleUniversity in the United Kingdom, says, “Umbilical cord blood stem cells give us lots of tissue.” His local hospital, for example, delivers 6,000 babies a year. “We have a cord blood bank,” McGuckin says, “and we’ve used that to transplant people who need new bone marrow.”
Despite all of the clinical interest in stem cells, basic scientists find them just as appealing. “One of the most exciting areas is the basic biology of how stem cells proliferate and make decisions between self-renewal and differentiation. Developmental biologists have grappled with these issues for a hundred years,” says Randall T. Moon, professor of pharmacology, Howard Hughes Medical Institute investigator, and director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington in Seattle.
Still, Moon sees beyond the basics. “Tissue engineering is a fairly underutilized area,” he says. “Instead of growing cells for transplanting, you could take the cells and entice them to grow over scaffolds into a structure or organ in vitro and then transplant organs and tissues rather than cells into patients.” He says that bladders have already been made just that way and used in people.
The therapeutic use of stem cells, though, will apply to many organ systems. Olle Lindvall, professor of neurology at LundUniversity, started working in neuroscience nearly 30 years ago. He entered this field with an interest in repairing the brain. “From my perspective,” says Lindvall, “stem cell research - in the long term - can completely change our possibilities to repair the brain and do something for many neurological patients where we have nothing today.”
Rules and Regulations
For research purposes, stem cells come under three general categories: human embryonic stem cells, adult human stem cells, and those from other organisms. Using human embryonic stem cells raises the most contention, because they must be collected from an embryo. “There really aren’t any issues in doing research with adult stem cells,” says Sherley. “They come from an adult donor, and you can get informed consent.” Moreover, obtaining these cells causes little if any harm to the donor. Even in cases like aspirating cells from the bone marrow, which carries some risk, many people volunteer to provide cells in this way.
Still, virtually all countries regulate the use of human stem cells, and the rules vary from country to country. “In the United Kingdom,” says McGuckin, “we can work on virtually any type of stem cells, but the work we do is very tightly regulated by law.” For example, to work on human embryonic stem cells, scientists in the United Kingdom must obtain a license and justify how the cells will be used.
“The diversity of attitudes across Europe,” say McGuckin, “is amazing. Some countries are okay with working on all sorts of stem cells, and some countries are not.” For example, Poland allows no work on human embryonic stem cells. McGuckin adds, though, that all European countries allow work on stem cells from umbilical cord blood. “With umbilical cord blood,” says McGuckin, “it is usually just thrown away.”
In Sweden, scientists enjoy an open view about stem cells. “We can do research on human embryonic stem cells, fetal stem cells, and there is also the possibility to use nuclear transfer for therapeutic purposes,” Lindvall explains.
When it comes to human embryonic stem cells, U.S. scientists with federal funding can only study lines approved by the National Institutes of Health. Nonetheless, scientists can use private or state funding to develop new lines, and some are doing that. In fact, some studies require embryonic stem cells instead of just adult ones. “Research indicates,” says Moon, “that adult stem cells do not do everything that you want them to do for developing therapies.” For example, embryonic stem cells can make any other type of cell, and adult stem cells cannot.
Donley says that access to human embryonic stem cells is good. She adds that her institute has distributed more than 400 batches of cells to researchers around the world, and the requests are increasing. She says, “Researchers under our agreement can do research in any area and are not restricted in patenting or publishing.”
Training for the Task
Smith believes that only a small number of researchers possess a credible record of work in this field. “Just billing yourself as a stem cell biologist doesn’t mean that someone is really in this field,” he says. “You must research where you are going to study, if you want to get good training in this field.”
Cellular and molecular programs provide a good start, but scientists can come from many other backgrounds. For example, Donley says, “We have scientists who specialize in mass spectrometry, and they do lots of studies on the proteins and growth factors that keep cells undifferentiated or cause them to differentiate.”
At the Genome Institute of Singapore, Liu and his colleagues take a genomics approach to understanding the transcriptional regulation of embryonic stem cells. Consequently, scientists there need a background in cellular and developmental biology. Liu adds, “A key skill has become computer analysis. So computational biology is becoming an important facet of the research.”
In fact, the road ahead for basic research on stem cells will cover many topics: controlling stem cells, learning how they divide and mature, and creating techniques to influence stem cells to make particular cells. “We need people interested in developmental biology, basic cell biology, and molecular biology,” says Lindvall. “That will be very, very important.” He adds that scientists skilled in imaging will also be in demand for research on stem cells. “They will help us follow what is happening in the body with these cells,” he says. Although Lindvall sees basic research as today’s most pressing need, he also believes that clinical and basic scientists should work together to create a roadmap to the clinic
In addition, research on adult stem cells is expected to grow quickly. “These cells can go into people more easily,” says McGuckin. “In America and across Europe, more money is going into adult stem cells, bit by bit.” Some examples already exist for using these cells. McGuckin mentions the use of bone marrow stem cells to treat people with a myocardial infarction, where the heart gets starved for blood. “These people need to grow new blood vessels in the heart,” says McGuckin, “and bone marrow stem cells have the ability to do that.” Moreover, he points out that stem cells from an umbilical cord can treat many diseases right now. He says, “People with leukemia often need radiation and chemotherapy, and then they need a new blood system. Cord blood can give them that.” He and his colleagues are also developing a treatment for liver diseases that uses stem cells from cord blood. This work requires a broad scientific team.
Beyond bench skills, Lindvall says that stem cell scientists need a knowledge of ethics. He says, “I ask my new students about their view on the ethical aspects of working on stem cells. If they see none, that is negative from my perspective.” He adds, “We need to balance between many aspects.”
Stem Cell Skills
“You need the same basic skills that any other area of biology requires,” says Smith. “You have to be really interested in understanding a fundamental property of the cells.” He adds, “A lot of people come with the motivation - that may be laudable - that they may want to cure a particular disease, but then they should be working in a hospital, because the science is not at that stage yet.”
Moon believes that working on stem cells goes beyond scientific capabilities. When asked what skills make a young scientist desirable for work in this field, he laughs before saying, “patience.” Moon adds, “You need to look at it as an investment in the long haul. There are no quick answers here and no quick therapies.” He points out that it took scientists about 15 years to make bone marrow transplants safe and effective. “If you are interested in developing therapies,” says Moon, “you need a long-term view that it may take a decade or more for these to emerge.” Also, work in this area demands even more than patience. To work toward stem cell therapies, a scientist also needs exposure to bioethics, bioengineering, and technologies like microfluidics and nanotechnology.
Stem cell research also takes a fair amount of specialized training. “Stem cells are extremely difficult to grow,” says Moon, “and there’s a long learning curve.” As a result, Moon believes that scientists in this field must firmly believe that the work can enhance basic biology and, eventually, benefit patients. He adds, “For anyone who can survive that learning period, I think there will be lots of great jobs.”
Despite the specialization, stem cell research requires the basics, as well. Sherley thinks that a young scientist needs a core knowledge of cellular and molecular biology - understanding the lab techniques and the analytical approaches. “Then,” he says, “you can bring a lot of other technologies to bear on that core training.” For instance, an electrical engineer with a knowledge of biology could develop tools for in vitro or in vivo analysis of stem cells. “There will always be a need for more tools,” Sherley says. Without an understanding of cellular and molecular biology, though, Sherley mentions that lots of things can go wrong. “You can spend a lot of time making a device,” he says, “and then later find out that it is not effective for the cells.”
So thinking ahead never hurts. “This field also demands critical thinking, maybe more so than some others.” Sherley says, “There’s a lot of misinformation out there, because this field is evolving.” So stem cell scientists must read the historical and current literature, process the information, and then come up with the best ways to advance the field.
An Academic Consensus
When asked where today’s stem cell jobs lie, Smith says, “I’d say in all spheres, but not in huge numbers in bioindustry or hospitals.” He adds, “In the academic sector, people are crying out for stem cell researchers. In fact, lots of people are moving fields to work on them.” Smith also expects the growth in stem cell research to generate more jobs in the future.
The good news is that stem cells cover lots of ground, from molecular biology and biotechnology through cell transplantation and therapy. “It means that people can come into stem cell biology from more or less any field,” says Smith. In fact, Smith does not even recruit people who have already worked on stem cells. Instead, he looks for people who could bring expertise from other areas, like neurobiology or proteomics. He says, “You don’t have to do your Ph.D. in stem cells to get a postdoc in the area.”
Nonetheless, stem cells do not make an easy career. “Like any research, it’s bloody hard at times,” Smith says, “and just because it’s trendy that doesn’t make it any easier to do the science.” In fact, he thinks that the trendy side might make this field even more difficult. “There is more noise, more bad science,” Smith says. “It can be confusing to see the wood from the trees.”
In terms of jobs, though, academics looks like the dominant home for stem cell research now and in the near future. “I don’t really have any quantitative data,” Sherley says, “but my sense - from who I see at meetings and so on - is that the No. 1 source will be university labs.” He believes that large pharmas are looking for stem cell scientists to add expertise, but he doesn’t see large efforts there yet. On the other hand, he points out that some small biotechnology companies and many government labs do seek stem cell scientists.
The United States already possesses hot spots for stem cell research. Moon says that California universities will have the most jobs. He also points to programs at HarvardUniversity, the University of Wisconsin, Madison, and the University of Michigan. Moon’s own University of Washington in Seattle just created the Institute for Stem Cell and Regenerative Medicine, which already has 80 labs and is presently constructing a building and receiving private grants in the millions. Moon says, “We are already one of the few places that is successful in raising private money.”
The academic trend does not affect the United States alone. Looking at jobs in Sweden, Lindvall says: “It’s, of course, academia at the moment. I think currently there is less enthusiasm in industry. There are companies, but as the field develops there will be more business opportunities related to stem cells.” He points out that scientists will patent devices - say, for sorting stem cells - that will lead to new business opportunities, as well.
The opportunities in academics, though, are growing. Donley points out that stem cell scientists at the University of Wisconsin, Madison, grew from one in the late 1990s to about 80 today.
A Bright Future
Overall, research on stem cells will grow and generate new opportunities ahead. “I’d say it is probably one of the brightest areas in biology and medicine,” says Moon.
From both basic and applied perspectives, stem cells already teach scientists new things at an increasing rate. No one knows how far stem cells can take modern science, but some researchers expect huge changes. “Instead of cutting something out by surgery or treating diseases only with drugs,” Moon says, “people may eventually get at least part way to where a starfish has been all along: If it loses an arm, it grows one back. We may not be able to regrow arms, but we can certainly entertain the goal of leveraging knowledge of stem cells to improve treatments for diseases and injuries.”