UCSD Biological Sciences Builds Stem Cell Research Team
Hardly a week passes without stem cell research entering into the national spotlight. Fascinating to some and frightening to others, stem cells have recently emerged as a promising and controversial research field. Human embryonic stem cells hold the most potential to alleviate suffering and simultaneously generate the most heated debate. Since they are “pluripotent,” meaning they can give rise to any type of cell found in the adult body, embryonic stem cells could possibly be used to replace tissues damaged by injury or disease. However, the process of creating a culture of embryonic stem cells results in the destruction of a human embryo. This trade-off, the destruction of a human embryo for the benefit of an adult, lies at the heart of the ethical controversy surrounding stem cell research and leads some people to question whether such research should be undertaken at all.
A possible alternative to embryonic stem cells are adult stem cells, populations of cells found in adults that can give rise only to limited types of cells. Instead of pluripotent, they are labeled as “multipotent.” For example, the hematopoetic stem cells found in bone marrow can give rise to any type of blood cell, but cannot become other cell types, such as neurons. Adult stem cells are difficult to obtain and even more difficult to grow in a culture, but they can be used without destroying an embryo, meaning their use presents a much smaller ethical dilemma than the use of embryonic stem cells. Much more research is necessary to fully evaluate the advantages and disadvantages of using embryonic versus adult stem cells.
In 2001, embryonic stem cell research encountered a major hurdle when President Bush decided the trade-off was not justifiable and restricted federal funding for research that results in the destruction of human embryos. In November 2004, the people of California decided otherwise with the passage of Proposition 71, which established the California Institute for Regenerative Medicine and which will provide roughly $300 million annually over ten years for stem cell research. This funding will make possible the research into embryonic stem cells necessary to better evaluate their potential for medicinal use.
The prospect of regenerative medicine is a principal driving force behind stem cell research. One of the ultimate goals is to transplant stem cells into a person who has suffered tissue damage from an injury or illness, for example, replacing neurons destroyed by Parkinson’s disease, growing new pancreatic cells to combat diabetes, or repairing damage to the heart caused by cardiovascular disease. Much more knowledge of stem cells must be gained, however, before those procedures become feasible. In the more immediate future, basic research into stem cell development will facilitate a greater understanding of birth defects and many types of cancer, leading to better treatment and possibly preventing these maladies. In addition, human stem cells could be used to grow organs in vitro, enabling more efficient pre-clinical drug testing and eliminating some of the need for animal studies.
Two fundamental questions must be addressed before regenerative medicine becomes a reality: How do stem cells remain stem cells? and How do stem cells become other types of cells? Each time a stem cell divides, it either stays in the stem cell state (a process known as self-renewal) or becomes more specialized (a process known as differentiation). In order to safely and efficiently use stem cells to replace lost tissue, researchers first need to fully understand the external signals that determine whether a stem cell will self-renew or differentiate and the internal signaling pathways and genes involved in carrying out that decision. Understanding these signals is absolutely essential. Incomplete understanding could result in the failure of transplanted cells to generate the appropriate tissue, or worse, in the uncontrolled growth of cells, leading to cancer.
Stem cell research is very much in its infancy. Now that sufficient funding is available, UCSD hopes to become a leading contributor to understanding stem cell biology. The Division of Biological Sciences is involved in campus-wide and regional efforts to advance stem cell research. In conjunction with the Salk Institute for Biological Studies, the Burnham Institute, and the Scripps Research Institute, UCSD has tentative plans to apply for funds from Proposition 71 to build a major research facility dedicated to stem cell research. Since the details of Proposition 71 are not yet sufficiently defined to devise concrete plans, no time frame for this project has been set. For the more immediate future, a central stem cell facility is being established in the UCSD School of Medicine’s Cancer Center. The focus of this facility will include generating and maintaining new human embryonic stem cells as well as providing training for researchers interested in working with those cells. Because human stem cells intended for use in human subjects must be kept separate from animal cells, smaller satellite facilities throughout the campus will provide local access points where researchers can carry out experiments with human stem cells. The Division of Biological Sciences, for example, will establish such a facility in Bonner Hall.
“The goal of the Division,” says Dean Eduardo Macagno, “is to establish a group of four to six laboratories that address the basic questions of stem cell biology.” This group will be composed of current faculty whose research involves stem cells and newly recruited faculty. A search is currently underway for two investigators with experience in embryonic stem cell research, and is expected to conclude within a year.
Dr. David Traver, who joined UCSD Biological Sciences in 2004, has set up a lab to study stem cells, specifically the hematopoetic stem cells that give rise to the immune system and blood cells in zebrafish. As a model system, zebrafish offer unique advantages for studying stem cells. To begin with, fertilization occurs externally, and the resulting embryos are transparent, meaning the very first stages of development can be directly observed as they naturally occur. By using transgenic fluorescent markers, it should be possible to fully characterize the differentiation of pluripotent embryonic stem cells into multipotent, hematopoetic stem cells.
“The major focus of the lab,” says Traver, “is to do very simple imaging experiments, to try to figure out how these cells behave in their natural microenvironment.” Research such as this will provide a means to fully understand the entire process of differentiation, from pluripotent stem cells through the successive stages of specialization down to individual cell types. Mapping the developmental fate of blood cell lineages will not only enable better treatments for blood and immunological disorders but also lay the foundation for understanding the differentiation of all other cell types.
Dr. Steven Briggs came from Diversa Corporation to join the UCSD Biological Sciences faculty in 2004. One goal of his laboratory is to take a holistic approach to studying the regulation of genes involved in the control of stem cell identity. Using a novel modification of chromatin-immunoprecipitation combined with mass spectrometry, his lab will identify the full complement of proteins bound to a gene at a given time. Starting with genes known to be involved in stem cell fate, the differences in protein composition between pluripotent stem cells and differentiated cells will shed light on how those genes are regulated as well as lead to new genes. In Brigg’s words, “The hope is to create a regulatory network that integrates both the environmental niche and the developmental program of the cell, because the intersection of those two will play a large part in determining the fate of the cell.”
In addition, several labs have interests that intersect stem cell research at various levels. According to Dr. Anirvan Ghosh, whose lab works on the establishment of neuronal connections during development, “All biologists have something to contribute to the stem cell problem.”
Ideally, UCSD will establish a broad-based, cross-disciplinary approach to stem cell research. As the understanding of the advantages and disadvantages of embryonic versus adult stem cells becomes clearer, the debate over the ethical implications of regenerative medicine can proceed in a more informed manner.
More information on the research being conducted in the Traver lab.
UCSD has set up a website that provides detailed information on the various stem cell programs and activities being conducted by UCSD and other area research institutions. Topics include: faculty experts, teacher/student resources, stem cells in the news, stem cell 101, seminars and events, policy and ethics issues, and more.
Contributing Writer: Paul Kennedy Mueller
From BioSphere Magazine, Fall 2005 issue, page 13.