Scientists Create Customized Stem Cells
# Took 242 Donated Human Eggs To Grow One Batch
May 19, 2005 3:05 pm US/Eastern
WASHINGTON (AP) South Korean scientists have created the world's first human embryonic stem cells that are customized to injured or sick patients, a major step in the quest to grow patients' own replacement tissue to treat diseases.
These same scientists last year became the first to clone a human embryo, sparking international clamor. But those cloned stem cells ?- the building blocks that give rise to every tissue in the body were a genetic match to a healthy woman, not a sick person. And it wasn't easy: It took 242 donated human eggs to grow just one batch.
Now the Seoul scientists have cloned patient-specific stem cells, important if doctors are to develop cell-based therapies that won't be rejected by the body's immune system. The technique worked with males and females, as young as 2 and as old as 56 ?- all suffering either spinal cord injuries, diabetes or a genetic immune disease, the researchers report in Friday's edition of the journal Science.
And the Korean lab found faster and safer ways to cull stem cells, using far fewer donated eggs ?- about 20 per try. They also eliminated use of mouse "feeder cells" that have been used to nourish most human stem-cell lines, thus easing concerns about contamination.
Any therapy is still years away from being tested in people.
"Therapeutic cloning has tremendous, tremendous healing potential, but we have to open so many doors before human trials," lead researcher Hwang Woo-suk of Seoul National University said in a telephone interview. "Our work reveals the possibility that this technology could be applied in the patient himself in the future."
Stem-cell specialists called the research remarkable.
"This is a very important advance," said Dr. Janet Rowley of the University of Chicago, a genetics specialist who helped co-author recent ethics guidelines on stem-cell research from the Institute of Medicine. "It's surprising to me the amount of progress they've made in basically a year's time."
"This paper will be of major impact," said stem-cell researcher Dr. Rudolph Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass. "The argument that it will not work in humans will not be tenable after this."
The work marks "a gigantic advance" for another reason, said neuroscientist Fred Gage of the Salk Institute for Biological Studies in San Diego. By cloning stem cells from sick patients, scientists can watch, in a test tube, the very earliest origins of diseases like Alzheimer's, insight that could point to other ways to prevent and treat illness, explained Gage, who plans to do some of that work.
The Korean research "will be a tremendous boon to the investigation of the nature and biology of human disease," he said.
It's also sure to revive international controversy over whether to ban all forms of human cloning, as the Bush administration wants ?- or to allow cloning for medical research, so-called therapeutic cloning that South Korea has committed by law to pursue.
Culling stem cells destroys the days-old embryo harboring them, regardless of whether that embryo was cloned or left over in a fertility clinic. Because opponents argue that is the same as destroying life, President Bush has banned federally funded research on all but a handful of old embryonic stem-cell lines ?- and the South Korean work spotlights the frustration many U.S. scientists felt at being left behind.
"It's just going to highlight the tragedy of our current situation in America where there are technologies that are promising that are not being pursued by talented American scientists because of ideologic constraints," Rowley said.
The Seoul researchers collected eggs donated by 18 unpaid volunteers and removed the gene-containing nucleus from them. They inserted into those eggs DNA from skin cells of 11 people who had spinal cord injuries, Type 1 diabetes or a congenital immune disease.
Chemicals jump-started cellular division, and 31 blastocysts ?- early-stage embryos ?- successfully grew. From those, the scientists were able to harvest 11 colonies, or "lines," of stem cells, each one a genetic match to the patient who had donated a skin snippet.
The scientists were careful to explain to the research participants that getting medicine made from their stem cells is a long shot. They don't yet know how to control which types of tissues ?- brain cells, bones, muscles, etc. ?- the stem cells form, something the Korean lab is studying next.
"I didn't think they would be at this stage for decades, let alone within a year," said Dr. Gerald Schatten of the University of Pittsburgh, who acted as an adviser to the Korean lab in analyzing its data for U.S. publication. "All of us in the biomedical communities owe our colleagues in Korea a tremendous debt of gratitude."
The work raises ethical concerns, cautioned Stanford University bioethicists David Magnus and Mildred Cho. Scientists must ensure that women understand they get no benefit and can be put at some risk when they agree to donate eggs for medical research ?- and that patients who volunteer also understand that it's unlikely they'll benefit from any stem cells they help to clone because so many years of research are yet required, they wrote.
(© 2005 The Associated Press. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. )
The Stem-Cell Also-Ran: America
The Bush Administration's restrictions on U.S. research will inflict major pain down the road as other countries keep advancing
It's a great time to be a stem-cell researcher -- unless you're working in most U.S. laboratories. In quick succession, foreign labs have announced a series of major breakthroughs, developments that move scientists a step closer to cures for a range of illnesses. On May 20, British researchers revealed that they had cloned a human embryo. The same day, a Korean team announced success in creating stem cells from embryos cloned from people with diseases. Such cells could then theoretically be used as treatments for those people. And earlier this year, Japanese researchers reported that they had used stem cells to cure Parkinson's-like disease in monkeys.
Advertisement
These overseas triumphs are a reminder that restrictions on federal funding for stem-cell research in the U.S., as well as many state and federal threats to ban much of the research, are hindering the pace of research in America. As part of an ongoing lobbying effort, 37 university presidents and chancellors sent Congress a letter on May 23, arguing that progress in foreign labs is "an indication that U.S. scientists are being hobbled in their pursuit of cures and therapies using this promising research."
A day later, the House of Representatives passed a bill that would relax the limits on research. But with President George W. Bush threatening to veto the bill if it clears Congress, it looks like U.S. researchers will have to resign themselves to "playing catch-up," says Charles Jennings, executive director of the Harvard Stem Cell Institute, which has raised $30 million in private funding.
CONSTANT THREAT. One advantage foreign scientists have is higher levels of government funding. Korea alone is estimated to be spending more than $100 million a year on embryonic stem-cell work, compared to a paltry $24 million last year from the National Institutes of Health. In addition, several countries, such as Korea and Britain, explicitly allow the creation of human embryos as a source of stem cells. In the U.S., there's a constant threat that such an approach could be banned.
As a result, researchers fear the U.S. is at a serious competitive disadvantage. The effects won't be seen immediately. It will take years for researchers to learn how to transform stem cells into new heart muscle, neurons, pancreatic cells, or other key tissues consistently enough to meet Food & Drug Administration requirements for the safety of new treatments.
But the research will have more shorter-term applications, such as creating cells that the pharmaceutical industry can use to test new drugs. And already, researchers are staking claims to valuable intellectual property. By falling behind, experts say, the U.S. could lose out on the eventual commercial applications to companies in Korea, Singapore, India, and other countries that are rushing ahead with the science.
"MODEL-T" CELLS. That would be a stunning reversal, since the field was pioneered in the U.S. American researchers were the first to create long-lived cultures of stem cells, called "stem-cell lines" in 1998, and the scientific community immediately saw vast potential. Stem cells are undifferentiated progenitors -- able to become many different parts of the body. Researchers believe, for example, it should be possible to transform stem cells into the insulin-producing cells that are lost in diabetes, or the dopamine-making neurons lost in Parkinson's Disease, thus curing those illnesses.
But in August, 2001, Bush, citing an aversion to destroying human embryos in the process of extracting stem cells, restricted federally funded research to only existing stem-cells lines. That had a chilling effect on research in the U.S. Those cell lines created before August, 2001-- of which only 22 are useful -- are "the model-T versions," explains Dr. Robert Goldstein, chief scientific officer at the Juvenile Diabetes Research Foundation, which now gives two-thirds of its grant money for embryonic stem cell research to foreign scientists.
The bill passed by the House would allow scientists to create more cell lines from thousands of embryos now slated for destruction at in vitro fertilization clinics. While that could bring several hundred more stem-cell lines into play, the bill "is like getting a foot in the door and trying to open it a little, when other countries are building huge gates," says cloning expert Jose Cibelli, professor of animal biotechnology at Michigan State University.
TALENT DRIVE. And Bush vows to veto the bill anyway. "I made it very clear to the Congress that the use of federal money, taxpayers' money, to promote science which destroys life in order to save life is -- I'm against that," Bush reminded reporters just last week.
The outlook isn't totally bleak. The federal government is spending several hundred million dollars on work with stem cells in mice and with adult stem cells. And some states and private funders are stepping into the void left by the federal government on human embryonic stem cells. Last November, California voted to spend $3 billion over 10 years. The Harvard Stem Cell Institute has raised $30 million from foundations and private donors, and is creating its own stem-cell lines. The Starr Foundation is giving $50 million to three New York City research centers over three years for stem-cell work.
The support is enabling U.S. scientists to continue to make significant strides. At Johns Hopkins stem-cell pioneer John Gearhart is successfully creating heart cells that could be used to treat heart disease. "You cannot underestimate the talent present in this country," says Gearhart. "This is the group that has led the world."
These efforts will keep the U.S. in the game -- but not in the unchallenged lead. "We're really in the Dark Ages," charges Cibelli. "We're failing at the core -- at providing the federal money that would lead to new biotechnology and new companies able to take this to patients." Unless the Administration changes its stance, many breakthroughs will continue to come from outside the U.S.
The University of Texas Health Science Center at Houston News Room
UTHSC-H Home [ Contact Us ] [ People Directory ] [ Maps ] [ University A-Z ] [ Calendars ] [ Site Map ]
Search News Releases
UT Scientists Develop Promising New Procedure
To Differentiate Human Embryonic Stem Cells
HOUSTON - (Feb. 26, 2007)?-Molecular scientists at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) - which is part of the University of Texas Health Science Center at Houston - have developed a new procedure for the differentiation of human embryonic stem cells, with which they have created the first transplantable source of lung epithelial cells.
The process, created in the laboratory of Rick A. Wetsel, Ph.D., a professor of molecular medicine at the IMM, is described in this week's edition of the Proceedings of the National Academy of Sciences (PNAS). Research scientist Dachun Wang, M.D., is lead author of the article, "A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells."
"We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells," said Wetsel, noting the procedure also can be used to create other types of highly-specialized cells.
Scientists at the IMM used the in vitro method to create lung epithelial cells known as alveolar epithelial type II. The cells were derived from a human embryonic stem cell line approved by the National Institutes of Health (NIH).
The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene.
"It is a general technology for developing select cells from human embryonic stem cells," said C. Thomas Caskey, M.D., the IMM's chief operating officer, director and CEO-elect. "The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others."
James T. Willerson, M.D., president of the UT Health Science Center at Houston, said " I believe this is an important development by the Wetsel laboratory at the IMM. I look forward to seeing its transitional impact."
Alveolar epithelial type II cells are called "the stem cells of the lungs" because of their versatility and many important functions. They produce proteins including surfactant that inflates lungs. They also make other cells lining the inner lung. "They regulate lung fluids and oxygen levels," Wetsel said.
The cells are part of the tiny air sacs lining the lower airways known as alveoli. Tissue thin, they transfer oxygen into the blood and remove carbon dioxide. If the walls of the hundreds of millions of alveolus in a pair of lungs could be spread out and placed side by side, they would cover the floor of a classroom.
According to Wetsel, transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries. "These are the cells that can potentially be used for regenerative lung repair," he said.
Hereditary lung disorders most likely to benefit from transplantation of alveolar epithelial type II cells include respiratory distress syndrome of the newborn, alpha-1 related emphysema and cystic fibrosis, Wetsel believes. "All three of these diseases are caused by single gene defects and therefore have been logical candidates for gene therapy," Wetsel said.
Respiratory distress syndrome of the newborn, a condition affecting premature infants less than 37 weeks of age, may be caused by a genetic mutation triggering a surfactant shortage. Likewise, alpha-1 related emphysema, a condition affecting 100,000 Americans, results from an inherited deficiency of alpha-1 antitrypsin. Further, cystic fibrosis is the second most common childhood onset inherited disorder in the United States.
Transplantable alveolar epithelial type II cells may also one day be helpful in the treatment of other lung diseases including chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States, claiming the lives of 122,283 Americans in 2003, and asthma, Wetsel said.
Still years away from their use in regenerative medicine, Wetsel said the next step involves research trials with mice.
Other IMM investigators participating in the study included David L. Haviland, Ph.D., assistant professor in the Center for Immunology and Autoimmune Diseases, and Eva Zsigmond, Ph.D., assistant professor and associate director of the IMM's Laboratory for Developmental Biology.
Funding for the study of the NIH-approved human embryonic stem cell line was provided by Houston philanthropists Clive and Nancy Runnells.
The most comprehensive academic health center in the Southwest, the UT Health Science Center at Houston is home to six schools devoted to medicine, nursing, public health, dentistry, health informatics and graduate studies in biomedical science. In addition to the IMM, other components are the UT Harris County Psychiatric Center and the Mental Sciences Institute. The UT Health Science Center at Houston, founded in 1972, is part of the University of Texas System. It is a state-supported health institution whose state funding is supplemented by competitive research grants, patient fees and private philanthropy.
Media Contact: Rob Cahill
Media Hotline: 713-500-3030
Site Policies | Contact Us
Copyright 2002-Present
He has PD as does my friend Dan from whom I have heard nothing.
