The University of California, San Francisco this week has begun distributing the first of its two human embryonic stem cell lines to academic researchers, increasing the opportunity for scientists around the world to study the therapeutic potential of the cells.
The UCSF cells are being sent to nine academic researchers in the United States and two in England, the total number of scientists who, to date, have completed formal requests to study the cells. The scientists include ten from universities and one from the National Institutes of Health. Approximately 30 additional inquiries from the United States, Europe and Asia have been made to study the cells, but the applications have not yet been submitted. The University expects to receive additional requests for the cells during the next year.
The hope is that studies on the basic biology of human embryonic stem cells will provide insights that could lead to the use of these cells in cell-transplantation therapy, to treat such diseases as diabetes, heart disease, Parkinson's disease and Alzheimer's disease.
UCSF is one of only two academic institutions in the United States that produced human embryonic cells lines that qualified for inclusion on the National Institutes of Health Human Embryonic Stem Cell Registry http://escr.nih.gov/, established by President George Bush in August 2001. The cell lines included on the registry can be studied by academic researchers with federal funds.
The studies that led to the development of the two stem cell lines were conducted with funding from Geron Corporation, a biotechnology company in Menlo Park, California, with a matching grant from BioSTAR, a University of California program that forges partnerships among University of California scientists and businesses.
"This is a very exciting day for UCSF, and a significant one for stem cell biology research," says Regis B. Kelly, PhD, UCSF executive vice chancellor, office of research. "The best way to determine the therapeutic potential of embryonic stem cells is to foster research efforts in many laboratories, and the role of University labs in this effort is critical, as there is less need to focus on financial implications."
"We are very pleased to be able to share these cells with other academic researchers. The effort that has gone in to getting these cells ready for distribution has been worthwhile. Studying the basic biology of embryonic stem cells is a key step in exploring their therapeutic potential," says Meri Firpo, PhD, UCSF assistant research geneticist in the Department of Obstetrics, Gynecology and Reproductive Sciences.
Firpo led the team that derived the two cell lines in the UCSF laboratory of Roger Pedersen, PhD, at that time UCSF professor and research director, reproductive genetics unit, Department of Obstetrics, Gynecology and Reproductive Sciences, and now at the University of Cambridge, in England.
Firpo and her colleagues derived the two lines of embryonic stem cells in the winter and spring of 2001. The cells were obtained from three to five day old embryos that had been left over following fertility treatments and had been donated for research. The cells were then developed into cell "lines," large quantities of genetically identical cells created by replication initiated with a single cell in the laboratory dish.
Last fall and winter, following the establishment of the NIH Human Embryonic Stem Cell Registry, the University of California Office of the President and UCSF negotiated mutually agreeable terms with several institutions for sharing the cells with academic researchers. The negotiations took place with Geron, which funded the research and holds the exclusive commercial license to the two stem cell lines; WiCell Research Institute, a nonprofit subsidiary of Wisconsin Alumni Research Association, which holds the patent on the technology used to derive the cells; and the National Institutes of Health, which will fund research conducted by recipients of UCSF's two cell lines. The terms of the agreement are reflected in a Materials Transfer Agreement (MTA) that researchers interested in studying the UCSF cell lines must complete.
In May, Firpo received a two-year, $800,000 Infrastructure Grant Award from the NIH to prepare the cells lines for distribution, which has involved hiring and training a team of technicians to grow the cells, establishing an administrative system for distributing them, and training visiting scientists from other labs to grow the cells. The grant also funds some basic science studies on the cells.
UCSF is currently distributing the first cell line it derived (HSF-6). Academic researchers who wish to study the cells must complete the materials transfer agreement accessible at the UCSF web site http://escells.ucsf.edu/ and send a payment of $5,000, which partially covers the costs of preparing and shipping the cells. The team will prepare the second cell line it derived, HSF-1, for distribution in the next year.
Scientists routinely produce large quantities of various cell types in the petri dish. However, preparing, or "expanding," a large quantity of human embryonic stem cell lines for distribution is a technically challenging task.
"These are touchy, finicky cells requiring lots of hands on work," says Firpo.
In addition to funding the production of the cell lines, Firpo's NIH Infrastructure grant award funds studies aimed at improving the biological conditions for growing embryonic stem cells. All of the cell lines included on the NIH Human Embryonic Stem Cell Registry have been grown on mouse cells and exposed to animal protein for their growth and maintenance, and thus could have been contaminated with pathogens. This could make them less likely to be acceptable for transplantation into people. While scientists can still learn a great deal by studying these cells, the ultimate goal is to grow the cells without exposure to bovine serum or products that have been exposed to mouse cells.
"Our first priority has been to get these cells ready for distribution for basic science studies. But we're also very interested in improving the conditions for growing the cells so that they could prove useful for cell transplant therapy," says Firpo.
In an additional effort, UCSF researchers are also working to derive new lines of human embryonic stem cells. These studies are being conducted at an off-campus site that does not receive federal funds. As with the original two cell lines, the researchers are working to derive cells from embryos that have been left over following fertility treatments in fertility clinics and have been donated for the research.
The goal of these additional studies is to develop methods for deriving and maintaining embryonic stem cells without exposure to mouse and bovine factors and to increase the number of cell lines that could some day be used for cell transplantation. Some scientists believe a large number of cell lines would be needed in cell transplantation therapy to match the genetic variation of a diverse population of people.
Funding for this research is supported in part by Geron Corp., with a matching grant from the University of California BioSTAR program, as well as by the Juvenile Diabetes Foundation. The principal investigator of the BioSTAR grant is Susan Fisher, UCSF professor of stomatology, anatomy and pharmaceutical chemistry. Firpo is co-PI on the BioSTAR grant and leads the Juvenile Diabetes Foundation grant.
The current human embryonic stem cells is emblematic of a broader stem cell initiative at UCSF. Last month, the University announced the establishment of a major new endeavor, the Developmental and Stem Cell Biology Program. The goals of the program are to consolidate and promote a broad range of investigations regarding cell development, specifically cell "determination" and "differentiation," the defects in those processes that give rise to disease, and the potential for stem cell therapy in the treatment of disease. The intent is to consolidate the already existing strength in UCSF's labs and to expand those efforts into a focused program.
The program was launched in August with the announcement of Intel chairman Andy Grove's $5 million matching grant to fuel the new UCSF Stem Cell Discovery Fund. The "Grove Stem Cell Challenge," is intended to fund basic studies in stem cell biology and their translation into clinical practice.
UCSF has a long tradition in the field of embryonic stem cell research. In addition to the human embryonic stem cell research initiated by Roger Pedersen, UCSF developmental biologist Gail Martin, PhD, co-discovered embryonic stem cells in mouse studies in the early 1980s, and coined the term. Developmental biologist Didier Stainier, PhD, is pioneering studies of embryonic stem cells in zebrafish, identifying genes that contribute to the development of heart stem cells. And neurologist Arturo Alvarez-Buylla, PhD, recently discovered the origin of the human brain's stem cells, and is exploring whether it is these cells that, when cancerous, lead to brain tumors.
"There is an enormous opportunity to investigate and understand developmental and stem cell biology at levels ranging from fundamental processes to the treatment of disease, and UCSF seeks to be at the forefront of that field both in the laboratory and in the clinic," says Keith Yamamoto, PhD, UCSF School of Medicine vice dean for research.