EMBARGOED FOR RELEASE 4 P.M. EST, NOV. 5
CONTACT: Terry Devitt, (608) 262-8282, [email protected]
Editor's Note: To obtain a copy of the human embryonic stem cell paper that will be published in the Nov. 6 issue of the journal Science, contact the American Association for the Advancement of Science News & Information Office at (202) 326-6440. The embargo set by Science is 4 p.m. EST Thursday, Nov. 5. Stem cell photos, laboratory B-roll video in Betamax format, a computer animation, and graphics are available through the UW-Madison Office of News & Public Affairs at (608) 262-8282 or (608) 262-3571. An electronic press kit can also be found on the UW-Madison News & Public Affairs web site at http://www.news.wisc.edu/emediakit. Audio actualities for radio reports can be obtained by calling (608) 263-4576.
WISCONSIN SCIENTISTS CULTURE ELUSIVE EMBRYONIC STEM CELLS
MADISON - The dream of one day being able to grow in the laboratory an unlimited amount of human tissues for transplantation is one step closer to reality.
Writing in the journal Science, a team of scientists from the University of Wisconsin-Madison report the successful derivation and prolonged culture of human embryonic stem cells - cells that are the parent cells of all tissues in the body.
The achievement has profound implications for transplant medicine, drug discovery and basic developmental biology. It opens the door to growing from scratch everything from heart muscle to bone marrow and brain tissue.
The work "shows you can derive and culture these cells, and it opens the possibility for some dramatic new transplantation therapies," said James A. Thomson, a UW-Madison developmental biologist and the lead author of the report published today (Nov. 6) in the nation's leading scientific journal. "Although a great deal of basic research needs to be done before these cells can lead to human therapies, I believe that in the long run they will revolutionize many aspects of transplantation medicine."
The work, which was supported by the Menlo Park, Calif.-based biotechnology company Geron Corp., caps a 17-year international race to be the first to capture and sustainably culture human embryonic stem cells. By providing the raw material for virtually every kind of human tissue, new customized strategies for treating a wide range of human diseases including diabetes, heart disease, some forms of cancer, and Parkinson's disease can now be developed.
For example, many diseases, such as Parkinson's and juvenile onset diabetes mellitus, occur because of the death or dysfunction of just one of a few cell types. The replacement of those cells would offer lifelong treatment. To treat heart disease, heart muscle cells could be injected directly to shore up failing heart tissue.
Such clinical applications are years - perhaps more than a decade - away.
The embryonic stem cells were derived from the inner cell masses of donated human blastocysts. A blastocyst is a hollow ball of about 140 cells that develops several days after fertilization.
The embryos from which the blastocysts developed were produced in a laboratory dish for clinical purposes, prepared to assist couples having difficulty achieving pregnancy. They were left over after successful clinical procedures to treat infertility, and in cooperation with the UW-Madison Medical School's department of obstetrics and gynecology, were donated specifically for this project with the informed, written consent of the patients.
Thomson's team established five independent cell lines and has been able to grow them indefinitely in culture. They have observed the cells to differentiate into the three primary germ lines that make up the body - endoderm, ectoderm and mesoderm - and subsequently into arrays of tissue cells such as cartilage, bone, muscle, neural and gut cells.
For biologists, these cell lines offer insights into developmental events that cannot be studied directly in the human embryo, but which have important clinical consequences for birth defects, infertility and pregnancy loss, said Thomson. Moreover, a more complete understanding of normal development will ultimately allow the prevention or treatment of abnormal human development.
The most likely immediate application of human embryonic stem cell technology, according to Thomson, would be strategies to quickly screen hundreds of thousands of chemicals for effective medicines. By measuring how pure populations of specific differentiated cells respond to potential drugs, it would be possible to sort out drugs that may be both useful or problematic in human medicine.
The Wisconsin Alumni Research Foundation (WARF), an independent, not-for-profit corporation that manages patents on behalf of the University of Wisconsin-Madison, has applied for a patent on the human embryonic stem cell technologies described in today's Science article and Geron Corp. has a license to develop the technology. The company has invested significantly in the long quest for human embryonic stem cells. In addition to supporting the efforts at Wisconsin, it has funded other groups doing similar work at Johns Hopkins University and at the University of California at San Francisco.
Because there is a prohibition on the use of federal money for such research, federal funds were not used to support the stem cell work at Wisconsin.
"Our hope is that these cells could be grown in the laboratory and then used to regenerate failing tissue," said Thomas Okarma, Geron vice president for research and development. "Because these cells do not age, they could be used to generate virtually a limitless supply of cells and tissue for transplantation."
While the Wisconsin scientists have been able to capture and culture undifferentiated human embryonic stem cells, their transformation into different types of cells cannot yet be directed. Under certain culture conditions the embryonic stem cells differentiate, but the differentiation is to a random, mixed population of cells.
Finding ways to direct the human embryonic stem cells to become specific cells of clinical importance is an important next step required before new therapies can be developed.
Ways to prevent the immune system from rejecting transplanted cells also need to be developed. However, banking embryonic stem cells with records of genetic compatibility, or genetically altering cells to reduce or combat immune rejection, are two potential strategies for overcoming the problem, said Thomson.
Thomson's group is now actively pursuing collaborations with clinical scientists and transplant surgeons to perform the basic research needed to ultimately develop human embryonic cell-based therapies. Among those is Jon Odorico, a UW-Madison transplant surgeon, who cited the potential of human embryonic stem cells to be used in very focused ways to repair or replace damaged or diseased tissues or organs.
"The principal theoretical advantages of this type of treatment for organ replacement over current organ transplantation is the fact that the cells can be grown in large quantities, helping to negate the problem of the limited supply of donor organs, and can be genetically engineered outside the body to escape immune attack," Odorico said.
These "experiments have opened up some exciting new areas of research for transplant surgeons," he added.
Co-authors of the paper published today include Joseph Itskovitz of the Rambam Medical Center, Haifa, Israel; Sander S. Shapiro, Michelle A. Waknitz, Jennifer J. Swiergiel, Vivienne S. Marshall and Jeffrey M. Jones, all of UW-Madison.
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- Terry Devitt (608) 262-8282, [email protected]
************** FACT SHEET Embryonic stem cells Fall 1998
*** What are embryonic stem cells?
All embryonic stem cells are undifferentiated cells that are unlike any specific adult cell. However, they have the ability to form any adult cell. Because undifferentiated embryonic stem cells can proliferate indefinitely in culture, they could potentially provide an unlimited source of specific, clinically important adult cells such as bone, muscle, liver or blood cells.
*** Where do embryonic stem cells come from?
Human embryonic stem cells are derived from in vitro fertilized embryos less than a week old. These embryos were produced for clinical purposes, but were no longer wanted for implantation by the couples who donated them. They were donated specially for this project with the informed consent of donors. In virtually every in vitro fertilization clinic in the world, surplus embryos are discarded if they are not donated to help other infertile couples or for research. The research protocols were reviewed and approved by a UW-Madison Institutional Review Board, a panel of scientists and medical ethicists who oversee such work.
*** Why are they important?
Embryonic stem cells are of great interest to medicine and science because of their ability to develop into virtually any other cell made by the human body. In theory, if stem cells can be grown and their development directed in culture, it would be possible to grow cells of medical importance such as bone marrow, neural tissue or muscle.
*** What, precisely, has the UW team accomplished?
Scientists have been attempting to isolate and culture human embryonic stem cells for more than a decade. Using 14 blastocysts obtained from donated, surplus embryos produced by in vitro fertilization, the Wisconsin group established five independent cell lines. The cell lines, derived from preimplantation stage embryos, were capable of prolonged, undifferentiated proliferation in culture and yet maintained the ability to develop into a variety of specific cell types, including neural, gut, muscle, bone and cartilage cells.
*** How might they be used to treat disease?
The ability to grow human tissue of all kinds opens the door to treating a range of cell-based diseases and to growing medically important tissues that can be used for transplantation purposes. For example, diseases like juvenile onset diabetes mellitus and Parkinson's disease occur because of defects in one of just a few cells types. Replacing faulty cells with healthy ones offers hope of lifelong treatment. Similarly, failing hearts and other organs, in theory, could be shored up by injecting healthy cells to replace damaged or diseased cells.
*** Are there other potential uses for these cells?
The first potential applications of human embryonic stem cell technology may be in the area of drug discovery. The ability to grow pure populations of specific cell types offers a proving ground for chemical compounds that may have medical importance. Treating specific cell types with chemicals and measuring their response offers a short-cut to sort out chemicals that can be used to treat the diseases that involve those specific cell types. Ramped up stem cell technology would permit the rapid screening of hundreds of thousands of chemicals that must now be tested through much more time-consuming processes.
*** What can these cells tell us about development?
The earliest stages of human development have been difficult or impossible to study. Human embryonic stem cells will offer insights into developmental events that cannot be studied directly in humans in utero or fully understood through the use of animal models. Understanding the events that occur at the first stages of development has potential clinical significance for preventing or treating birth defects, infertility and pregnancy loss. A thorough knowledge of normal development could ultimately allow the prevention or treatment of abnormal human development. For instance, screening drugs by testing them on cultured human embryonic stem cells could help reduce the risk of drug-related birth defects.
*** If a cluster of these cells was transferred to a woman, could a pregnancy result?
No. These cells are not the equivalent of an intact embryo. If a cluster of these cells was transferred to a uterus, they would fail to implant, and would fail to develop into a fetus.
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