Funding of Stem Cell Research: Policy Statement
and Guidelines.
Human pluripotent stem cells are a unique scientific and medical resource. In 1998, University of Wisconsin and Johns
Hopkins University scientists isolated and successfully cultured human pluripotent stem cells. The pluripotent stem cells derive from
early stage embryos donated by couples undergoing fertility treatment, as well as non-living fetuses from terminated first-trimester
pregnancies. Informed consent was obtained from donors in both cases, and women donated fetal tissue only after deciding to
terminate the pregnancies.
Since pluripotent stem cells are needed for nearly all cell types of the body – muscles, nerves, heart, and blood – they hold
great promise for research and health care. This advance in human biology generates enthusiasm among scientists, patients suffering
from diseases such as cancer, heart disease and diabetes, and the patients’ families.
Further research using human pluripotent stem cells may help:
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Generate cells and tissue for transplantation. Pluripotent stem cells possess the ability to develop into specialized cells that
can be used as replacement cells and tissues to treat diseases and conditions such as Parkinson’s Disease, spinal cord
injuries, strokes, burns, heart diseases, diabetes, osteoarthritis and Rheumatoid Arthritis.
Improve understanding of normal human development and the causes of defects and cancer.
Change the way we develop drugs and test them for safety. Drugs – rather than being evaluated for safety on an animal
model, may be initially tested on cells developed from pluripotent stem cells. The safest candidate would then advance to
animal testing, followed by human testing.
The Need for Guidelines to Govern Research Using Pluripotent Stem Cells
The NIH is prohibited from using any appropriated funds for "... (1) the creation of a human embryo or embryos for
research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of
injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.208(a)(2) and section 498(b) of the Public
Health Service Act (42 U.S.C. 289g(b))."
Since there is enormous potential for human pluripotent stem cells to aid medical research, the NIH asked the General
Council of the Department of Health and Human
Services (DHHS) to determine whether research utilizing pluripotent stem cells is permissible under existing federal law governing
embryo and fetal tissue research. After consideration, the DHHS concluded that because human pluripotent cells are not
Embryos. Current federal law does not prohibit DHHS funds from being used for research utilizing these cells.
While recognizing the ethical and legal issues surrounding human pluripotent stem cell research and the need for stringent
oversight of this class of research - oversight that goes beyond the traditional rigorous NIH scientific peer review process - the NIH
issued a moratorium on the funding of this research until guidelines could be developed and an oversight process could be
implemented.
In April 1989, the NIH convened a working group of the Advisory Committee to the Director (ACD), NIH, to provide
advice to the ACD relevant to guidelines and oversight for this research. The working group and included scientists, clinicians,
ethicist, lawyers, patients, and patient advocates. During its deliberations, the group considered advice from the National Bioethics
Commission, the public, and scientists. Draft guidelines for this research were published for public comment. After review and
consideration of all comments, the NIH Guidelines for Research Using Human Pluripotent Stem Cells (NIH Guidelines) were
published in the Federal Register and became effective on August 25, 2000.
Specifics of the Guidelines
The purpose of the NIH Guidelines is to set forth procedures to help ensure that
NIH-funded research in this area is conducted in an ethical and legal manner. By issuing these guidelines, the NIH aims to enhance
both the scientific and ethical oversight of this area of research and the pace at which scientists can explore its many promises. These
guidelines will encourage openness, provide appropriate federal oversight, help to make certain that all researchers can make use of
these research tools, and assure full public access to the practical medical benefits of research using these cells.
US Government Approves New Testing of Embryonic
Stem Cells
NEW YORK (AP) – For only the second time, the U.S. government has approved a test in people of a treatment using embryonic stem
cells – this time for a rare disease that causes serious vision loss.
Advanced Cell Technology, a biotechnology company based in Santa Monica., Calif., said the research should begin early next year,
following the green light from the U.S. Food and Drug Administration. Just last month another biotech company, Geron Corp., said it
had begun preliminary testing in people for treating spinal cord injuries by injecting cells derived from embryonic stem cells.
Scientists hope to use stem cells to create a variety of tissues for transplant. But human embryos have to be destroyed to harvest those
cells, which has made their use controversial.
ACT’s experiment will focus on Stargardt disease, which affects only about 30,000 Americans. But the company hopes the same
approach will work for similar and more common eye disorders like age-related macular degeneration, which affects millions.
Stargardt is an inherited disorder that attacks central vision used for tasks like reading and recognizing faces. Some patients go totally
blind, even losing peripheral vision, while others are severely impaired and can only perceive light or see their hands moving in front
of their faces.
The disease typically starts in adolescence. The key problem is that impaired scavenger cells fail to remove toxic byproducts from the
eye, allowing them to build up and kill other cells. There is no proven treatment. In the new study, 12 patients will be treated with
healthy scavenger cells, created in a laboratory from human embryonic stem cells. This early phase of the research is primarily to test
the safety of various doses, injecting only one eye of each patient.
“We’re also hoping to see some improvement in visual acuity, but that’s a bonus,” said Dr. Robert Lanza, ACT’s chief scientific
officer.
The research will be performed at medical centers in Massachusetts, New Jersey and Oregon, ACT said. Stephen Rose, chief research
officer of the Foundation Fighting Blindness, said his group is “very, very glad” that ACT has permission to begin the study.
Scientists Create Human Liver from Stem Cells
LONDON (Reuters) - Scientists have for the first time created a
functional human liver from stem cells derived from skin and blood and
say their success points to a future where much-needed livers and other
transplant organs could be made in a laboratory.
While it may take another 10 years before lab-grown livers could be used to treat patients, the
Japanese scientists say they now have important proof of concept that paves the way for more
ambitious organ-growing experiments.
"The promise of an off-the-shelf liver seems much closer than one could hope even a year ago," said
Dusko Illic, a stem cell expert at King's College London who was not directly involved in the research
but praised its success.
He said however that while the technique looks "very promising" and represents a huge step forward,
"there is much unknown and it will take years before it could be applied in regenerative medicine."
Researchers around the world have been studying stem cells from various sources for more than a
decade, hoping to capitalize on their ability to transform into a wide variety of other kinds of cell to
treat a range of health conditions.
There are two main forms of stem cells - embryonic stem cells, which are harvested from embryos,
and reprogrammed "induced pluripotent stem cells" (iPS cells), often taken from skin or blood.
Countries across the world have a critical shortage of donor organs for treating patients with liver,
kidney, heart and other organ failure. Scientists are keenly aware of the need to find other ways of
obtaining organs for transplant.
The Japanese team, based at the Yokohama City University Graduate School of Medicine inJapan,
used iPS cells to make three different cell types that would normally combine in the natural formation
of a human liver in a developing embryo - hepatic endoderm cells, mesenchymal stem cells and
endothelial cells - and mixed them together to see if they would grow.
They found the cells did grow and began to form three-dimensional structures called "liver buds" - a
collection of liver cells with the potential to develop into a full organ.
When they transplanted them into mice, the researchers found the human liver buds matured, the
human blood vessels connected to the mouse host's blood vessels and they began to perform many of
the functions of mature human liver cells.
"To our knowledge, this is the first report demonstrating the generation of a functional human organ
from pluripotent stem cells," the researchers wrote in the journal Nature.
Malcolm Allison, a stem cell expert at Queen Mary University of London, who was not involved in
the research, said the study's results offered "the distinct possibility of being able to create mini livers
from the skin cells of a patient dying of liver failure" and transplant them to boost the failing organ.
Takanori Takebe, who led the study, told a teleconference he was so encouraged by the success of this
work that he plans similar research on other organs such as the pancreas and lungs.
A team of American researchers said in April they had created a rat kidney in a lab that was able to
function like a natural one, but their method used a "scaffold" structure from a kidney to build a new
organ.
And in May last year, British researchers said they had turned skin cells into beating heart tissue that
might one day be able to be used to treat heart failure.
That livers and other organs may one day be made from iPS cells is an "exciting" prospect, said
Matthew Smalley of Cardiff University's European Cancer Stem Cell Research Institute.
"(This) study holds out real promise for a viable alternative approach to human organ transplants," he
said.
Chris Mason, a regenerative medicine expert at University College London said the greatest impact of
iPS cell-liver buds might be in their use in improving drug development.
"Presently to study the metabolism and toxicology of potential new drugs, human cadaveric liver cells
are used, " he said. "Unfortunately these are only available in very limited quantities".
The suggestion from this new study is that mice transplanted with human iPS cell-liver buds might be
used to test new drugs to see how the human liver would cope with them and whether they might have
side-effects such as liver toxicity.
(This story refiles to fix a typo in the name "Yokohama" in the eighth paragraph)
(Reporting by Kate Kelland; Editing by Janet Lawrence)