Scientists Move Closer to Ability to Grow Tissue
In a stunning first step toward producing donor tissue and organs for transplants on demand, two groups of researchers have grown human cells with the potential to become virtually any kind of body tissue.
These “stem cells” are the parent cells from which all organs in the body are produced. The ability to grow them in large quantities in the laboratory opens the door to new treatments for a broad variety of diseases, including heart disease, cancer, diabetes and degenerative brain disorders.
The researchers have already demonstrated that the stem cells can be converted into other types of cells, including bone, muscle, neural and gut cells. However, they have not yet deciphered the programming required to order the cultured cells to become, for example, a kidney or even a mass of brain or pancreatic cells.
But the discoveries, to be reported today in Science and next week in the Proceedings of the National Academy of Sciences, will make it much easier to explore such approaches.
The cells will also provide new tools for screening potential drugs and for examining the early stages of embryo development, which are still highly mysterious in humans. The cells do not, however, have the ability to grow into fetuses.
“This finding is really quite remarkable,” said Lana Skirboll, director of the Office of Science Policy at the National Institutes of Health. “This is the first time we have had a replicating human stem cell line.”
Experts cautioned, however, that it may be a decade or longer before cells suitable for transplant are available, and longer before complete organs can be grown.
“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 transplantatation medicine,” said biologist James A. Thomson of the University of Wisconsin, who led one of the teams.
One major barrier to rapid exploitation is that researchers who rely on federal funding may not be able to use the tissues because they are derived from a human embryo.
Thomson and his colleagues isolated stem cells from 10-day-old embryos left over from attempts at artificial fertilization. The crux of their research was devising the proper mix of nutrients and environmental conditions to allow the cells to proliferate in the lab--a feat researchers have been striving to achieve for nearly two decades.
National Institutes of Health lawyers will gather soon to study both the cells and the law forbidding the use of federal funds to study embryos--updated just last month in the new budget bill--and determine whether federally funded researchers can experiment on the cells, Skirboll said. “I have no idea how this will play out,” she added.
The new research was all privately funded to avoid such restrictions, with the bulk of the money coming from the Geron Corp. of Menlo Park, which retains the right to exploit the discovery. Geron is supporting at least two other teams of researchers who are also close to growing human stem cells.
“Our hope is that these cells will be grown in the laboratory and then used to regenerate failing tissue,” said biologist Thomas Okarma, Geron’s 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 tissues for transplantation,” he added.
Among the diseases that could potentially be treated are:
* Huntington’s and Parkinson’s diseases. Researchers have already shown in humans that transplanting fetal brain cells into such patients can lead to marked improvement. The new cell lines could provide a much larger source of cells.
* Heart disease. Research in mice has shown improvement in function when immature heart muscle cells are implanted into diseased heart tissue.
* Diabetes. Implants of pancreatic islet cells can cure diabetes, but the cells are in short supply. The cultured cells could provide a source of islet tissue.
* Cancer. Bone marrow transplants have proved valuable in treating many types of cancer, and the research could provide a new source of such marrow cells.
Before any of this can happen, experts cautioned, researchers have to learn how to control the genetically based process by which the stem cells develop into various types of tissues and organs. Biologists will also have to learn how to engineer the cells before they are implanted so that they will not be rejected by the recipient’s immune system. Both of those are major tasks.
The first uses of the cells, therefore, might be for screening new drugs. A batch of stem cells might be converted into heart cells, for example, and used to study both the beneficial and adverse effects of potential heart drugs.
This “could have a major impact on pharmaceutical research and development,” Okarma said.
Thomson’s team began its research with blastocysts, hollow balls containing about 140 cells that develop as a fertilized egg grows into an embryo. The blastocysts were created during the treatment of infertile couples, who donated them specifically for this project.
The researchers took a mass of stem cells from the interior of the blastocysts and placed them on dishes containing mouse “feeder” cells that provide nutrients. Years of work were required to identify the precise conditions that would allow the stem cells to keep reproducing without change, to yield a long-term supply of cells.
In the next step, the researchers found that varying the conditions under which the cells were grown yielded other types of cells that have more specific purposes, like muscle tissue. But the researchers have not yet been able to control this process.
Growing the cells “is a major technological achievement with great importance in human biology,” said geneticist John Gearhart of the Johns Hopkins University School of Medicine in a commentary in Science.
Gearhart and his colleagues have grown their own line of stem cells, but they took a different approach from Thomson. They searched through small samples of tissue from aborted fetuses to isolate cells called primordial germ cells, which would have eventually become either eggs or sperm.
They then put these primordial germ cells through a process similar to that used by Thomson, producing genuine stem cells. Geron officials say they are sensitive to public concerns about the use of fetal or embryonic cells in research and the company has its own panel of ethical advisors, headed by Karen Lebacqz of the Pacific School of Religion in Berkeley.
The panel approved the projects on the basis that Geron was making beneficial use of fetal tissue and fertilized eggs that would otherwise have been discarded or permanently frozen.
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Creating Cells
In the first major step toward producing human tissues and organs for transplant, Wisconsin researchers have grown human stem cells in the laboratory. Stem cells are valuable because they have the potential to grow into any other type of tissue.
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THE PROCESS
(1) Scientists separate an inner cell mass from a 10-day-old human embryo that was left over after artificial fertilization.
(2) The cell mass is placed in a culture dish, where it draws nutrients from irradiated white blood feeder cells from a mouse.
(3) After nine to 15 days, the cell mass is broken up into individual cells.
(4) The cells are spread out in a new culture dish with new feeder cells where they reproduce.
(5) Seven to 10 days later, the cells have produced several new lines of human embryonic stem cells.
SOURCE: GERON CORP.
