By David Bauman - Photos by Al Ferreira
The human body is made up of approximately 10 trillion or so cells of different types.
The cells wear out and must be renewed frequently in a continuous cycle of human biology.
Most chronic diseases occur because human cells either die or malfunction during this natural evolutionary process.
Stem cell therapies offer the promise of cell replacement to cure these chronic diseases.
The challenge facing scientists is to find out how these stem cells work naturally in the body, how they may be made to work better and potentially, how they may be re-programmed to work in new ways that repair damaged cells.
One reason for the tremendous excitement generated by human embryonic stem cells is their potential to develop into any kinds of tissue that make up the human body and its organs.
Because such complex research will take time and require long-term funding, scientists became concerned that their research would be curtailed when, in 2001, the White House announced restrictions on federal funding of embryonic stem cell research, limiting U.S. support to studies involving 64 existing stem cell lines and not for the creation of new stem cells specifically for the purpose of research.
However, with individual states having the authority to approve laws without similar funding restrictions, the Connecticut Legislature in 2005 approved legislation to fund human stem cell research.
State lawmakers thus positioned Connecticut to be at the forefront of stem cell research by committing $100 million for such research over the next 10 years and establishing a competitive process for awarding grants.
The Stem Cell Research Advisory Committee, chaired by J. Robert Galvin ’96 M.P.H., commissioner of public health in Connecticut, was appointed to distribute the funds based on the scientific, legal and ethical integrity of the work.
The first allocation last November of nearly $20 million includes 15 research proposals worth more than $12 million awarded to UConn faculty, or about 60 percent of the total funding, with the balance going primarily to Yale University and some to Wesleyan University.
The funds will support the work of 23 investigators at the Storrs and Health Center campuses.
“These awards recognize the expertise of several University of Connecticut faculty in a field of great promise to medical research and great potential to contribute to our state’s economic growth,” says UConn President Philip E. Austin.
“The University is playing a leadership role not only in the scientific aspects of stem cell research, as reflected by these awards, but in dealing with the ethical and philosophical issues.”
UConn’s leadership in biomedical research — the foundation for stem cell work — has been established through its major commitment in the field of regenerative medicine with the Center for Regenerative Biology at Storrs, which is led by Xiangzhong “Jerry” Yang, professor of animal science and one of the world’s leading experts on animal cloning.
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| Leann Crandall, manager of the stem cell laboratory at the UConn Health Center, examines embryonic human stem cells. |
Each day in a research laboratory located at the UConn Health Center, lab manager Leann Crandall unlocks a door for a closer look at the future of embryonic human stem cells. Inside the lab, nestled in a pair of incubators supplied with a constant carbon dioxide/oxygen gas mixture kept at human body temperature, lie glass plates on special copper shelving.
Each plate holds several million human embryonic stem cells in an amber-colored stew of nutrients, hormones, growth factors and blood serum that is required to keep the cells in their undifferentiated, “blank slate” state.
“They need care pretty much every day,” says Crandall. “You can’t just buy these cells and work on them,” says Crandall. “These are probably the most difficult cells in the world to cultivate.”
The challenge for Crandall is to maintain the stock cultures in their blank state and keep them from becoming one of the 220 cell types in our bodies.
This change process is known as differentiation, when cells evolve into a specific type of cell to begin the path of becoming a heart, finger bone or other part of the body. (Chart below.)
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| National Institutes of Health |
Crandall spends hours in the small sterile room carefully removing plates of cultured cells from the incubators to microscopically examine the cell colonies checking for bacterial infection, determining their state of “stemness” and refreshing the culture medium nurturing their growth.
“I liken it to weeding a garden,” she explains. “If you don’t keep control, if you don’t know what you’re looking for, they will start differentiating. It is, after all, what they want to do.”
Crandall spent years mastering the complicated cell culturing process under the tutelage of Ren-He Xu, a developmental biologist and renowned expert in growing human embryonic stem cells, whom she accompanied to UConn last year when he was recruited from the prestigious WiCell Research Institute to direct UConn’s stem cell lab.
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| Ren-He Xu, director of the UConn Stem Cell Institute. |
Xu, a founding member of the private Wisconsin Institute that first developed human embryonic stem cells, led the research team that was the first to culture the precious cells without the need for animal cells or products, long thought to be a source of potential contamination for their use in clinical settings.
Under Xu and Crandall, the laboratory is culturing, testing and banking eight stem cell lines, including some not approved by the National Institutes of Health for research, making UConn one of only a few universities in the nation and, with Harvard University, one of only two in New England that is growing such human embryonic stem cell lines.
Since arriving at UConn, Xu and Crandall have been at the forefront of bringing cutting-edge laboratory work to advance the human embryonic stem cell research community at UConn and provide the university with a critical bridge in bringing the promising cells out of the core lab and into other scientists’ research labs.
To anticipate and respond to ethical questions that may arise in this sensitive research, UConn created an Embryonic Stem Cell Oversight Committee (ESCRO) composed of scientific, ethical and legal experts and members of the community at large; ESCRO must approve all proposed stem cell research projects.
It is chaired by Anne Hiskes, associate professor of philosophy in the College of Liberal Arts and Sciences, who will lead the review of each project through a simply stated test: Are the anticipated benefits to human health greater than any potential risks to human dignity and the value of human life?
Capitalizing further on Connecticut’s commitment of public funds to stem cell research, UConn plans to establish the University of Connecticut Stem Cell Institute (UCSCI), separate from existing university facilities, in order to comply with U.S. government rules.
The plan includes relocating Xu’s human embryonic stem cell core lab to a renovated 113,000-square-foot facility located near the UConn Health Center.
Using $2.5 million the state awarded UConn to expand the stem cell core lab, Xu will develop additional human embryonic stem cell lines outside the federal guidelines and provide the associated training and expertise to researchers at the University and throughout Connecticut. UCSCI also will provide a campus-wide framework for collaboration among UConn geneticists, engineers, ethicists, chemists, pathologists, immunologists, oncologists, hematologists and scientists from other disciplines to unravel the mysteries of growth and development of adult and embryonic stem cells.
Several UConn scientists awarded the first grants from the state’s stem cell research fund are focusing on how to get cells ready for clinical use.
David Rowe, director for regenerative medicine and skeletal development in the UConn School of Dental Medicine and a stem cell scientist, is leading a diverse multidisciplinary team of researchers on a $3.5 million musculoskeletal project to understand how to get embryonic stem cells to help rebuild bone, cartilage, skin and muscle tissue.
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| Marc Lalande, associate dean for research planning and coordination at the UConn Health Center, meets with researchers. |
Joseph LoTurco, associate professor of physiology and neurobiology at Storrs, was awarded a $562,000 grant from the stem cell fund to study the genes that control the migration of stem cell-derived neurons in the brain.
In order to be useful in treating degenerative and traumatic brain disorders, embryonic stem cells that develop into neurons must be able to locate themselves in the correct area of the brain, he says.
Akiko Nishiyama, associate professor of physiology and neurobiology at Storrs, was awarded $530,000 to investigate the ability of different types of glial cells generated from human embryonic stem cells to promote regeneration in the brain.
Glial cells are thought to support the function of neurons, and some types of glial cells can promote the development of axons, which are extensions of neurons.
Citing the dozens of UConn researchers investigating stem cells as cures for disease that someday might be applied clinically, Marc Lalande, professor and chair of the department of genetics and developmental biology and associate dean for research planning and coordination at the UConn Health Center, calls stem cell research “a hugely complex yet immensely fascinating area of research with the potential to unlock probably the greatest scientific and medical discoveries ever.”
Notes Lalande, “We are still a long way from miracle treatments, but UConn is well positioned with a wide range of dedicated scientific teams to continue to be a pioneer in what could well be the most important research area of the 21st century.”
For more information, and a complete list of stem cell research projects at UConn, go to our Web site: http://stemcell.uconn.edu
The ethics of embryonic stem cell research
Anne Hiskes, associate professor of philosophy and former associate dean of the College of Liberal Arts and Sciences, is director of research, ethics and education for stem cell research. She is the chair of UConn’s Embryonic Stem Cell Research Oversight (ESCRO) Committee. She discussed the future of embryonic stem cell research with Karen Grava ’74 (CLAS).
What will the ESCRO Committee do?
The ESCRO is charged with developing ethical principles and policies for human embryonic stem cell research, reviewing and approving stem cell research protocols and educating investigators about ethical issues connected with human stem cell research. Our goals are to ensure that research is well justified and that inappropriate research does not occur.
Who is on the ESCRO Committee?
The membership of the committee includes faculty from Storrs and the Health Center with scientific, ethical and legal expertise; two community members and representatives from research compliance. Two of our
members are ordained clergy.
What are the concerns ethicists have about human stem cell research?
The origin of the human embryos is one of the biggest issues. The least ethically controversial source of embryos is excess frozen embryos developed for the purpose of having a family using in vitro fertilization (IVF).
If a couple decides that they no longer wish to keep their frozen embryos, they are given the opportunity to donate them to research instead of
discarding them. No human embryos may be donated for stem cell
research without fully informed and voluntary consent from the donors.
There is also the issue of whether it is ethical to create human embryos only for research purposes. People are concerned that this demeans human dignity and the inherent value of the human individual by creating human life simply for use as a research tool.
Ethical issues are also connected with the methods used to create embryos for research. Some people regard the use of somatic cell nuclear transfer — “therapeutic cloning” — as particularly problematic. There is an international ban on using nuclear transfer for human reproduction. Some people regard therapeutic cloning as particularly problematic because they see it as another step toward the engineering of human beings and reducing them to mere objects. Others see it as the first step toward using cloning for human reproduction.
Will there always be a need for ethical oversight of stem cell research?
There are always new ways of engineering the human genome and new ways of reprogramming DNA. There will always be new science and
technology that impact the basic processes associated with living and
dying. So regardless of the future of stem cell research, there will always
be a need for ethical oversight of biomedical research.
What precautions is UConn taking to ensure that our stem cell research
is ethical?
Any human embryonic stem cell research conducted at the University of Connecticut must follow protocols approved by the ESCRO. Researchers who violate accepted standards could lose their funding and be unable
to publish their findings. The best system is when researchers and the scientific community self-regulate with the guidance of nationally or
internationally accepted standards.