Category Archives: Oregon Stem Cells

When it comes to CRISPR, questions about if we can edit human embryos are fast giving way to discussions more focused on But should we? and When? as feats with the gene-editing technology have started to accrue.

Today, biologists from Oregon report in Nature that they have had unprecedented successes using that gene-editing technology to alter early-stage, viable human embryos. The advance moves the field far past earlier attempts by researchers in China and underscores the need to come up with some answersand fast, researchers say. Although the U.S. Food and Drug Administration is currently barred from granting approval to anyone hoping to use this technology in pregnancies, the Nature study suggests such work could be possible, says Jennifer Doudna of the University of California, Berkeley, a biochemist and CRISPR expert. But she and many others say this would be an inappropriate use of the technology. Im not categorically against all human germ-line editing, Doudna says, but I think there would need to be a reason to do it that would justify the risks and costs.

The Oregon Health & Science University team edited the DNA of dozens of embryos to correct for a genetic mutation that often leads to heart failure. They then checked the edited embryos with genome sequencing and discovered that the procedure caused no apparent errors. The group also managed to almost completely eliminate mosaicisman editing failure in which only some of the desired cells are repaired. Those are the things everyone was concerned about in earlier embryo work, says George Church, a CRISPR expert and geneticist at Harvard Medical School, who was not involved with the work.

The gene-editing success appears to be largely due to one procedural change: The researchers introduced the editing systemthe enzyme Cas9 and a guide RNA sequence that helps the editing machinery find its targetat the same time they injected the mutation-laden sperm into a healthy egg in the lab. That allowed for much earlier editing to take placeapparently prior to any cellular replication. Thats a departure from earlier approaches by other research groups in China that had instead introduced the editing components after the egg was fertilized by sperm. This small change in injection protocol has resulted in something better than all prior embryo work and cell culture work, Church says.

So far, preventing disease by employing CRISPRCas9 to alter the human germ linea human embryo, egg or spermhas remained extremely controversial, due to concerns about unwittingly introducing errors or leaving stowaway unedited disease-causing mutations that would put future generations at risk of disease. And until now CRISPR had not been tried on human embryos in the U.S. But Shoukhrat Mitalipov at Oregon and his colleagues went further than the earlier Chinese works, editing dozens of embryos with much greater efficiency.

This is a harbinger of whats to come, says Doudna, who also did not take part in the work. This underscores the important discussion that needs to happen right now, she says. George Daley, a stem cell researcher and dean of Harvard Medical School agrees: This paper establishes that we can do embryo gene editing. The question now remains should weand for what purposes and should there be certain applications that are allowed and others that are prohibited?

Such contentious issues were considered earlier this year by a National Academies of Sciences, Engineering and Medicine expert working group. It released guidance saying it would not be appropriate to proceed with any clinical work of human germ-line editing unless there was broad public consensus about the safety and merits of the worksomething that has not been achieved. The Academies committee has noted there is still a tremendous amount of research needed before trying to move forward with something like initiating pregnancies. And this Nature paper is just the beginning of the research the report contemplated, says legal scholar and bioethicist R. Alta Charo of the University of Wisconsin Law School, who co-chaired the Academies committee but says she is speaking for herself and not the panel. Understanding how gene editing works in human embryos will require research in human embryos, because mouse embryos, for example, have species-specific developmental differences, notes Dana Carroll, a biochemistry professor at the University of Utah who researches CRISPR. (The Mitalipov team only allowed the human embryos to proceed to the blastocyst stagewhen they are just a few days oldand did not attempt to implant them in a woman.)

In their study Mitalipov and colleagues edited out the MYBPC3 mutation associated with hypertrophic cardiomyopathy (HCM), a disease of the heart muscle that affects about one person in 500. Even a single copy of the mutation can result in the disorder and about 40 percent of individuals with HCM have the mutation. Right now the problematic gene can often be caught with preimplantation genetic diagnosisscreening of embryos in the labbut using CRISPR could boost the number of usable embryos, they say. Moreover, this CRISPR technique may eventually be an important intervention in situations where parents want to have a genetically related child but have a homozygous conditionsay both parents have two copies of a disease-causing mutation like that which causes sickle cellwhich would result in all embryos being affected by the disorder.

There are myriad technical obstacles to overcome before CRISPR could address homozygous conditions. One big one: Not everybody appreciates the way CRISPR technology worksit makes the cut in the DNA but it doesnt take care of the repairso we rely on the cells fundamental machinery to do that, Doudna says. In the latest experiments the Mitalipov group focused on snipping out the mutated gene in heterozygous cellsa situation in which there was still a good nonmutated copy available for the natural cellular repair systems in the embryo to use as a template for repair after the researchers edited out the problematic one. But in the course of their work, the team noted a potential hiccup for CRISPR work on homozygous forms of the disorderit may be extremely difficult to repair homozygous mutations once they are edited out because they would not have those built-in blueprints for what they should look like. In fact, the Mitalipov group found that cellular repair mechanisms, at least in their experiments, did not respond very well to the introduction of a synthetic repair template added by the researchers. According to Doudna, that suggests future homozygous work will be challengingmaybe far more so than scientists have expected.

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Embryo Gene-Editing Experiment Reignites Ethical Debate - Scientific American

Portland Business Journal

Meet the Oregon researcher whose embryo work is shaking the medical world Portland Business Journal Mitalipov conceded his stem cell research has always been controversial. " Anytime you have embryonic stem cells, always," he said. "We produce stem cells using eggs. That's always a controversial issue where are you going to get eggs? Even though ...

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Meet the Oregon researcher whose embryo work is shaking the medical world - Portland Business Journal

Theres still a way to go from editing single-cell embryos to a full-term designer baby. Credit: ZEISS Microscopy, CC BY-SA

The announcement by researchers in Portland, Oregon that they've successfully modified the genetic material of a human embryo took some people by surprise.

With headlines referring to "groundbreaking" research and "designer babies," you might wonder what the scientists actually accomplished. This was a big step forward, but hardly unexpected. As this kind of work proceeds, it continues to raise questions about ethical issues and how we should we react.

What did researchers actually do?

For a number of years now we have had the ability to alter genetic material in a cell, using a technique called CRISPR.

The DNA that makes up our genome comprises long sequences of base pairs, each base indicated by one of four letters. These letters form a genetic alphabet, and the "words" or "sentences" created from a particular order of letters are the genes that determine our characteristics.

Sometimes words can be "misspelled" or sentences slightly garbled, resulting in a disease or disorder. Genetic engineering is designed to correct those mistakes. CRISPR is a tool that enables scientists to target a specific area of a gene, working like the search-and-replace function in Microsoft Word, to remove a section and insert the "correct" sequence.

In the last decade, CRISPR has been the primary tool for those seeking to modify genes human and otherwise. Among other things, it has been used in experiments to make mosquitoes resistant to malaria, genetically modify plants to be resistant to disease, explore the possibility of engineered pets and livestock, and potentially treat some human diseases (including HIV, hemophilia and leukemia).

Up until recently, the focus in humans has been on changing the cells of a single individual, and not changing eggs, sperm and early embryos what are called the "germline" cells that pass traits along to offspring. The theory is that focusing on non-germline cells would limit any unexpected long-term impact of genetic changes on descendants. At the same time, this limitation means that we would have to use the technique in every generation, which affects its potential therapeutic benefit.

Earlier this year, an international committee convened by the National Academy of Sciences issued a report that, while highlighting the concerns with human germline genetic engineering, laid out a series of safeguards and recommended oversight. The report was widely regarded as opening the door to embryo-editing research.

That is exactly what happened in Oregon. Although this is the first study reported in the United States, similar research has been conducted in China. This new study, however, apparently avoided previous errors we've seen with CRISPR such as changes in other, untargeted parts of the genome, or the desired change not occurring in all cells. Both of these problems had made scientists wary of using CRISPR to make changes in embryos that might eventually be used in a human pregnancy. Evidence of more successful (and thus safer) CRISPR use may lead to additional studies involving human embryos.

What didn't happen in Oregon?

First, this study did not entail the creation of "designer babies," despite some news headlines. The research involved only early stage embryos, outside the womb, none of which was allowed to develop beyond a few days.

In fact, there are a number of existing limits both policy-based and scientific that will create barriers to implanting an edited embryo to achieve the birth of a child. There is a federal ban on funding gene editing research in embryos; in some states, there are also total bans on embryo research, regardless of how funded. In addition, the implantation of an edited human embryos would be regulated under the federal human research regulations, the Food, Drug and Cosmetic Act and potentially the federal rules regarding clinical laboratory testing.

Beyond the regulatory barriers, we are a long way from having the scientific knowledge necessary to design our children. While the Oregon experiment focused on a single gene correction to inherited diseases, there are few human traits that are controlled by one gene. Anything that involves multiple genes or a gene/environment interaction will be less amenable to this type of engineering. Most characteristics we might be interested in designing such as intelligence, personality, athletic or artistic or musical ability are much more complex.

Second, while this is a significant step forward in the science regarding the use of the CRISPR technique, it is only one step. There is a long way to go between this and a cure for various disease and disorders. This is not to say that there aren't concerns. But we have some time to consider the issues before the use of the technique becomes a mainstream medical practice.

So what should we be concerned about?

Taking into account the cautions above, we do need to decide when and how we should use this technique.

Should there be limits on the types of things you can edit in an embryo? If so, what should they entail? These questions also involve deciding who gets to set the limits and control access to the technology.

We may also be concerned about who gets to control the subsequent research using this technology. Should there be state or federal oversight? Keep in mind that we cannot control what happens in other countries. Even in this country it can be difficult to craft guidelines that restrict only the research someone finds objectionable, while allowing other important research to continue. Additionally, the use of assisted reproductive technologies (IVF, for example) is largely unregulated in the U.S., and the decision to put in place restrictions will certainly raise objections from both potential parents and IVF providers.

Moreover, there are important questions about cost and access. Right now most assisted reproductive technologies are available only to higher-income individuals. A handful of states mandate infertility treatment coverage, but it is very limited. How should we regulate access to embryo editing for serious diseases? We are in the midst of a widespread debate about health care, access and cost. If it becomes established and safe, should this technique be part of a basic package of health care services when used to help create a child who does not suffer from a specific genetic problem? What about editing for nonhealth issues or less serious problems are there fairness concerns if only people with sufficient wealth can access?

So far the promise of genetic engineering for disease eradication has not lived up to its hype. Nor have many other milestones, like the 1996 cloning of Dolly the sheep, resulted in the feared apocalypse. The announcement of the Oregon study is only the next step in a long line of research. Nonetheless, it is sure to bring many of the issues about embryos, stem cell research, genetic engineering and reproductive technologies back into the spotlight. Now is the time to figure out how we want to see this gene-editing path unfold.

Explore further: In US first, scientists edit genes of human embryos (Update)

This article was originally published on The Conversation. Read the original article.

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Editing human embryos with CRISPR is moving ahead now's the ... - Phys.Org

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A team of researchers has created the first genetically modified human embryos, the MIT Technology Review reported this week.

If the achievement is true - the scientists in question have neither confirmed nor disputed the account - it could mark a milestone in preventing transmission of genetic diseases instead of just treating them.

It would also rev up debate about the safety and ethics of genetically changing human beings, including what laws exist to safeguard patients and what constitutes a medically legitimate genetic modification.

The technology could be used to alter people for nonmedical purposes such as making them taller, giving them a specific eye shape or switching out their black hair for a shade of blonde - decisions that could be seen as fundamentally upending the definition of human nature.

The Technology Review story said the scientists harnessed the gene-editing method called CRISPR, a milestone in its own right, to modify one-celled embryos and allow them to develop for a few days. Other news organizations have published their own articles about this purported accomplishment, including the well-respected biomedical website Stat.

Prominent biologist Shoukhrat Mitalipov of Oregon Health & Science University was the lead researcher on the study, according to the Technology Review and Stat stories. Both reports said he declined to comment.

"Results of the peer-reviewed study are expected to be published soon in a scientific journal," Oregon Health & Science spokesman Erik Robinson said Thursday. He declined to specify what the study discovered.

The Technology Review story also said Jun Wu of the Salk Institute for Biological Studies in La Jolla, Calif., took part in the research. On Thursday, the institute declined to discuss the study.

Mitalipov gained fame in 2013 for spearheading development of the first human embryonic stem cells genetically matched to specific living individuals. The method he and some colleagues employed, called somatic cell nuclear transfer, was originally used two decades ago to create Dolly the cloned sheep.

Those researchers had taken a nucleus from a donor cell in a sheep and transferred it into a sheep egg cell that had had its own nucleus removed. The combination cell acted like a normal fertilized egg, producing Dolly. That sheep had the DNA of the donor cell, so it was a nearly exact clone of the sheep where the donor cell was taken from.

Growing a creature in this way is called reproductive cloning, and the U.S. government bans such procedures on people. Mitalipov and colleagues performed what is called therapeutic cloning: They used the process to cultivate human embryonic stem cells, which are likewise genetically matched to the donor nucleus.

In theory, these stem cells could be grown into replacement tissues to repair disease or injury in the person with the matching DNA. Genetically matching the stem cells to a particular patient lowers the risk that tissue transplants would be rejected by the person's immune system.

Wu and other Salk researchers in the lab of Juan Carlos Izpisua Belmonte have collaborated with Mitalipov to explore somatic cell nuclear transfer as a therapy for mitochondrial diseases. Mitochondria are organelles that make most of the energy cells use and perform other vital functions. They carry their own DNA.

The scientists generated human stem cells in the lab, repaired mitochondrial defects and found that they were able to restore certain desired functions in cells.

They took human skin cells and inserted their nuclei into human egg cells with healthy mitochondria that had their own nuclei removed. Those manipulated egg cells were then grown until they produced embryonic stem cells, free of the defective mitochondria.

The United Kingdom has approved a method that resembles reproductive cloning to prevent inheritance of mitochondrial diseases. This process involves replacing the nucleus of an egg cell from a donor with healthy mitochondria with that from the egg cell of the mother-to-be with diseased mitochondria.

Whether the reports this week about genetically modified human embryos are true, the capability of genetically engineering human embryos is fast approaching, said a bioethicist and a stem cell researcher who have examined the issue.

But having the capability doesn't mean it should be done, said Michael Kalichman, co-founding director of the the Center for Ethics in Science and Technology at the University of California, San Diego.

Kalichman said society isn't ready for genetically modifying humans, and that it's time for the public to start paying attention to what has been considered a futuristic scientific issue.

The strongest argument for genetic modification is to stop diseases, he said. The strongest argument against the technology is that it might cause unanticipated problems.

Paul Knoepfler, a stem cell researcher at UC Davis, said no matter how much effort is spent to ensure patient safety, there are no guarantees.

"The bottom line is that we'll never really know until someone tries it," Knoepfler said. Potential harm might not emerge until adulthood or even until the genetically altered people have their own children, he added.

"The other big thing is, I am not really convinced we can draw a clear line between doing this for only medical purposes versus (cosmetic) traits," he said.

Finally, it's not clear why genetically editing human embryos would even be needed to prevent transmission of a genetic disease, Knoepfler said.

"We already have an existing technology which is basically embryo screening," he said. Multiple embryos can be generated through in vitro fertilization to find one that doesn't have the disease.

"That would be much safer than actually doing an edit," he said.

Explore further: New research provides key insight about mitochondrial replacement therapy

2017 The San Diego Union-TribuneDistributed by Tribune Content Agency, LLC.

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Scientists genetically modify human embryos for first time, reports say - Medical Xpress

WASHINGTON (AP) Altering human heredity? In a first, researchers safely repaired a disease-causing gene in human embryos, targeting a heart defect best known for killing young athletes a big step toward one day preventing a list of inherited diseases.

In a surprising discovery, a research team led by Oregon Health and & Science University reported Wednesday that embryos can help fix themselves if scientists jump-start the process early enough.

It's laboratory research only, nowhere near ready to be tried in a pregnancy. But it suggests that scientists might alter DNA in a way that protects not just one baby from a disease that runs in the family, but his or her offspring as well. And that raises ethical questions.

"I for one believe, and this paper supports the view, that ultimately gene editing of human embryos can be made safe. Then the question truly becomes, if we can do it, should we do it?" said Dr. George Daley, a stem cell scientist and dean of Harvard Medical School. He wasn't involved in the new research and praised it as "quite remarkable."

"This is definitely a leap forward," agreed developmental geneticist Robin Lovell-Badge of Britain's Francis Crick Institute.

Today, couples seeking to avoid passing on a bad gene sometimes have embryos created in fertility clinics so they can discard those that inherit the disease and attempt pregnancy only with healthy ones, if there are any.

Gene editing in theory could rescue diseased embryos. But so-called "germline" changes altering sperm, eggs or embryos are controversial because they would be permanent, passed down to future generations. Critics worry about attempts at "designer babies" instead of just preventing disease, and a few previous attempts at learning to edit embryos, in China, didn't work well and, more importantly, raised safety concerns.

In a series of laboratory experiments reported in the journal Nature, the Oregon researchers tried a different approach.

They targeted a gene mutation that causes a heart-weakening disease, hypertrophic cardiomyopathy, that affects about 1 in 500 people. Inheriting just one copy of the bad gene can cause it.

The team programmed a gene-editing tool, named CRISPR-Cas9, that acts like a pair of molecular scissors to find that mutation a missing piece of genetic material.

Then came the test. Researchers injected sperm from a patient with the heart condition along with those molecular scissors into healthy donated eggs at the same time. The scissors cut the defective DNA in the sperm.

Normally cells will repair a CRISPR-induced cut in DNA by essentially gluing the ends back together. Or scientists can try delivering the missing DNA in a repair package, like a computer's cut-and-paste program.

Instead, the newly forming embryos made their own perfect fix without that outside help, reported Oregon Health & Science University senior researcher Shoukhrat Mitalipov.

We all inherit two copies of each gene, one from dad and one from mom and those embryos just copied the healthy one from the donated egg.

"The embryos are really looking for the blueprint," Mitalipov, who directs OHSU's Center for Embryonic Cell and Gene Therapy, said in an interview. "We're finding embryos will repair themselves if you have another healthy copy."

It worked 72 percent of the time, in 42 out of 58 embryos. Normally a sick parent has a 50-50 chance of passing on the mutation.

Previous embryo-editing attempts in China found not every cell was repaired, a safety concern called mosaicism. Beginning the process before fertilization avoided that problem: Until now, "everybody was injecting too late," Mitalipov said.

Nor did intense testing uncover any "off-target" errors, cuts to DNA in the wrong places, reported the team, which also included researchers from the Salk Institute for Biological Studies in California and South Korea's Institute for Basic Science. The embryos weren't allowed to develop beyond eight cells, a standard for laboratory research. The experiments were privately funded; U.S. tax dollars aren't allowed for embryo research.

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Genetics and ethics experts not involved in the work say it's a critical first step but just one step toward eventually testing the process in pregnancy, something currently prohibited by U.S. policy.

"This is very elegant lab work," but it's moving so fast that society needs to catch up and debate how far it should go, said Johns Hopkins University bioethicist Jeffrey Kahn.

And lots more research is needed to tell if it's really safe, added Britain's Lovell-Badge. He and Kahn were part of a National Academy of Sciences report earlier this year that said if germline editing ever were allowed, it should be only for serious diseases with no good alternatives and done with strict oversight.

"What we do not want is for rogue clinicians to start offering treatments" that are unproven, as has happened with some other experimental technologies, he stressed.

Among key questions: Would the technique work if mom, not dad, harbored the mutation? Is repair even possible if both parents pass on a bad gene?

Mitalipov is "pushing a frontier," but it's responsible basic research that's critical for understanding embryos and disease inheritance, noted University of Pittsburgh professor Kyle Orwig.

In fact, Mitalipov said the research should offer critics some reassurance: If embryos prefer self-repair, it would be extremely hard to add traits for "designer babies" rather than just eliminate disease.

"All we did is un-modify the already mutated gene."

This Associated Press series was produced in partnership with the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.

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First safe repair of disease-causing gene in human embryos - Virginian-Pilot

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News: VetStem Cell Therapy

Public release date: 23-Mar-2004 Contact: Jonathan Modie modiej@ohsu.edu 503-494-8231 Oregon Health & Science University

Oregon Stem Cell Center result of OHSU research strides New hub to focus on adult stem cells as organ transplant alternative PORTLAND, Ore. -- Oregon Health & Science University's fast-growing stem cell research program, which already has made significant strides in the hunt for human disease therapies, now has a place to call home. The multidisciplinary Oregon Stem Cell Center, the first of its kind in the Northwest, is studying cell and gene therapy as an alternative to organ transplantation for pancreatic and liver disorders, diabetes, cancer and a host of other human diseases. Its focus will be on adult stem cells.

Launched in January, the center is housed among several laboratories on the Marquam Hill Campus, but it will occupy a single floor in the 270,000-square-foot Biomedical Research Building now under construction and to be completed in fall 2005.

Its director, Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics in the OHSU School of Medicine, said the center is a hub for all areas of OHSU's rapidly expanding stem cell biology program. It aims to maximize the potential of various stem cells as therapies for human diseases through a rapid, "bench-to-bedside" approach involving basic research in stem cell biology and preclinical trials of therapies in animal models, followed by human trials.

"This is something we needed but didn't have," said Grompe, who has long studied gene and cell therapy for metabolic genetic diseases, as well as the molecular genetics of a rare, cancer-susceptibility syndrome called Fanconi anemia. "The consensus here at OHSU is that this is an area that is going to be important."

While the center's offerings will widen over time to cover other diseases -- Parkinson's disease and diabetes are considered "hot" areas of stem cell research -- it will concentrate on two areas for now and "build on that."

"My idea is to focus on the liver and the pancreas, and focus on adult stem cells," he said. "Our research already is advanced in liver reconstitution by stem cells and the repair of liver disease. We're clearly identified as one of the leaders in that area."

OHSU researchers like Grompe are wasting no time demonstrating the importance of stem cells. His laboratory is renowned as an international leader in cell therapy for liver and pancreas diseases as an alternative to organ transplantation.

Last year, Grompe published a study showing that bone marrow-derived stem cells from mice can combine with liver cells through cell fusion, which occurs when two or more cells combine to form one cell containing more genetic material than normal. The method reversed liver damage.

Other studies indicate bone marrow stem cells can meld with cells of other tissues, such as brain, spinal cord, lung, intestine and heart muscle.

The center's formation reflects a swell of research at OHSU involving stem cells. Scientists are conducting basic research, including molecular-level studies, in cardiology, endocrinology, genetics, hematology and oncology, neurology, neurological and general surgery, and reproduction.

"Basically all diseases which are currently being treated by organ transplantation are, at least on paper, amenable to cell therapy," Grompe said. "Our hope is that procedures as effective as whole organ transplantation will come out of (the center)."

Of particular interest to School of Medicine scientists are recently discovered clonally self-renewing stem cells. These unique cells have energized stem cell research - and are broadening the discipline's appeal to a larger group of scientists - because of their ability to generate copies of themselves and further divide into special-purpose offspring.

Clonally self-renewing stem cells come in several forms, such as mesenchymal stem cells, neural stem cells and multipotent progenitor cells, and can be used to create multiple cell types, including nerve cells, liver cells and muscle cells. They can be isolated from mice and primates, including humans, manipulated outside the living organism, and transplanted for reconstituting tissue.

"Their ability to be expanded in culture and then differentiated make them attractive for use in cell therapy," Grompe said.

Dan Dorsa, Ph.D., OHSU vice president for research and professor of physiology and pharmacology in the School of Medicine, said stem cells hold promise for treating many disorders. As a result, OHSU has the potential to make "a very broad impact."

"The use of stem cells for treating diseases will be at the forefront," Dorsa said. "The question we want to answer is: What is it about stem cells that allow them to be viable and take on the roles in the body you hope they will?"

The Oregon facility is one of only a handful of stem cell research centers around the country. Other sites include the University of Minnesota, Stanford University, the University of California, San Francisco, and the University of California, San Diego.

The heart of the center is three core facilities that provide cell development and management services for all campus research. They include:

-- A flow-sorting core to identify and isolate stem cell populations and characterize their progeny using fluorescence. Its primary tool, a fluorescence-activated cell sorter, "fishes out living stem cells and keeps them alive for transplantation and study," Grompe said.

-- A cell isolation core to culture, store and distribute specific stem cells. This will allow many researchers at OHSU rapid and easy access to professionally isolated and maintained, high-quality stem cell sources.

-- A monoclonal antibody production core to develop the large quantities of novel antibodies needed for identifying and purifying specific stem cells. Such a service has not been commercially available. "We'll be able to give cells to the core and get antibodies back for researchers," Grompe said. "And the antibodies don't have to be against stem cells to be effective."

The monoclonal antibody production core will be especially useful to cancer researchers, said Grover Bagby Jr., M.D., professor of molecular and medical genetics, OHSU School of Medicine, and director of the OHSU Cancer Institute.

"Having the capacity to make antibodies is going to be a nice core to have," he said. "I think a good number of cancer researchers will come to use that core. It'll be used right out of the gate."

And that could help scientists better track the progression of cancer, most forms of which are mutant outgrowths of stem cells.

"Understanding the cause of cancer definitely leads squarely into the ballpark of stem cells. We know it's true of leukemia and I suspect it's probably true of all other tissues," Bagby said. "There are a lot of things we can learn about stem cells that can lead to an understanding of how to protect them."

Dorsa and Grompe hope the center bolsters the development of OHSU-born spinoff companies while enhancing the university's partnerships with local and national biotechnology firms. It also could make OHSU more of a target for federal grants.

"There are very likely new industries that will be created by virtue of the new activity of the center," Dorsa said. The antibody core, for example, "will be attractive to commercialization."

The Oregon Stem Cell Center is funded by a three-year, $4.5 million grant from the Oregon Opportunity, the statewide, $500 million biomedical research funding initiative supported by public and private dollars. Three faculty members specializing in stem cell research also will be hired during the next two years.

Dorsa believes the Oregon Stem Cell Center fits in well with the National Institutes of Health's "Roadmap" initiative, which strives to accelerate fundamental discovery and translation of that knowledge into effective prevention strategies and new treatments.

"NIH dollars will be attracted by the stem cell center and the investments it will create," Dorsa said. "We think this one will be well positioned to compete for those dollars."

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Oregon Stem Cell Center to focus on adult stem cells as ...

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05/15/13Portland, Ore.

The breakthrough marks the first time human stem cells have been produced via nuclear transfer and follows several unsuccessful attempts by research groups worldwide

Update 05/23/2013: OHSU releases statement on questions about photos in stem cell paper. Read the statement.

Scientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. It is believed that stem cell therapies hold the promise of replacing cells damaged through injury or illness. Diseases or conditions that might be treated through stem cell therapy include Parkinsons disease, multiple sclerosis, cardiac disease and spinal cord injuries.

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. This latest research will be published in the journal Cell online May 15 and in print June 6.

The technique used by Drs. Mitalipov, Paula Amato, M.D., and their colleagues in OHSUs Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, is a variation of a commonly used method called somatic cell nuclear transfer, or SCNT. It involves transplanting the nucleus of one cell, containing an individuals DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.

A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells. Furthermore, because these reprogrammed cells can be generated with nuclear genetic material from a patient, there is no concern of transplant rejection, explained Dr. Mitalipov. While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine.

Another noteworthy aspect of this research is that it does not involve the use of fertilized embryos, a topic that has been the source of a significant ethical debate.

The Mitalipov teams success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs showed that human egg cells appear to be more fragile than eggs from other species. Therefore, known reprogramming methods stalled before stem cells were produced.

To solve this problem, the OHSU group studied various alternative approaches first developed in monkey cells and then applied to human cells. Through moving findings between monkey cells and human cells, the researchers were able to develop a successful method.

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