Category Archives: Wisconsin Stem Cells

Image courtesy of James Monaghan, Ph.D., Northeastern University, Boston, MA

BioPharmaceutical Technology Center 5445 East Cheryl Parkway Fitchburg/Madison, WI 53711 MAP & DIRECTIONS

OVERVIEW: The Symposium was coordinated by the Stem Cell & Regenerative Medicine Center, at the University of Wisconsin-Madison and the BTC Institute. It brought together leading researchers who are working in the areas of limb development and regeneration (morning session) and stem cells and tissue engineering (afternoon session).

HIGHLIGHTED ISSUES:

PRESENTERS

Jeremy Brockes, Ph.D., MRC Research Professor, Department of Structural and Molecular Biology, University College London, London, UK

David Butler, Ph.D., Emeritus Professor, Biomedical Engineering, University of Cincinnati, Cincinnati, OH

John Fallon, Ph.D., H.W. Mossman Professor Emeritus, Cell and Regenerative Biology Department, University of Wisconsin-Madison, Madison, WI (Moderator)

Johnny Huard, Ph.D., Professor, Departments of Orthopaedic Surgery, Microbiology and Molecular Genetics, Bioengineering, Pathology, Pediatrics, and Physical Medicine and Rehabilitation; Director of the Stem Cell Research Center, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA

Mayumi Ito, Ph.D., Associate Professor, The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, New York University School of Medicine, New York, NY

Timothy J. Kamp, M.D., Professor, Medicine; Co-director, Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison (Welcome)

Lisa Larkin, Ph.D., Associate Professor, Molecular & Integrative Physiology, Biomedical Engineering Department, University of Michigan, Ann Arbor, MI

Wan-Ju Li, Ph.D., Assistant Professor, Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health, Madison, WI

William Murphy, Ph.D., Harvey D. Spangler Professor, Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, Madison, WI

David Stocum, Ph.D., Professor and Dean Emeritus, Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN

Koji Tamura, Ph.D., Professor, Laboratory of Organ Morphogenesis, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan

Panagiotis Tsonis, Ph.D., Professor, College of Arts and Sciences: Biology, and School of Engineering: Bioengineering Graduate Program; Director, Center for Tissue Regeneration and Engineering, University of Dayton, Dayton, OH

Ray Vanderby, Ph.D., Professor of Biomedical Engineering & Professor of Orthopedic Surgery, University of Wisconsin-Madison, Madison, WI (Moderator)

SCHEDULE

ABSTRACTS

POSTER SESSION ABSTRACTS Congratulations to our Poster Contest winners: Thomas Lozito (1st place), David Belair (2nd place) and Ethan Lippmann (3rd place)!

For information regarding other past symposia, please visit our ARCHIVE

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WISCONSIN STEM CELL SYMPOSIUM - BTC Institute

Many diseases kill cells within organs, claiming lives or impairing a person's ability to live a normal life. For example, about 5.8 million Americans have heart failure and 670,000 people are diagnosed with it each year [source: Centers for Disease Control]. In heart failure, much of the heart muscle itself dies, so the heart cannot sufficiently pump blood.

Similarly, about 23.6 million Americans have diabetes [source: NIDDK, NIH]. Five to 10 percent of these people have Type I diabetes in which the insulin-producing cells of the pancreas are dead. Finally, about 1 million Americans live with Parkinson's disease [source: Parkinson's Disease Foundation]. In this disease, cells that make the neurotransmitter dopamine, which helps control movement, die. Patients with Parkinson's disease have tremors and uncontrollable movements. But what if these dead cells could be replaced with fresh cells? Could the patients be treated and live normal lives? That's the goal of stem cell research.

In this article, we'll look at stem cells, starting with the accompanying picture above. In the photo, the embryonic stem cell colonies are the rounded, dense masses of cells. The flat elongated cells are fibroblasts used as "feeder cells." We'll also find out how stem cells work, discover their potential to treat disease and get inside the ongoing debate surrounding their research and use. But first, let's cover some basics.

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How Stem Cells Work - HowStuffWorks

September 3, 2015

Tags: Weinberg LabStem Cells + Therapeutic CloningCancer

CAMBRIDGE, Mass. In the breast, cancer stem cells and normal stem cells can arise from different cell types but tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.

Deadly tumor-initiating cells seed metastases throughout the body and cause relapses in patients. Whether these tumor-initiating cells can also be referred to as stem cells, specifically, cancer stem cells, has been up for debate. The question is not purely one of semanticsthe label connotes scientists understanding of those cells identity and inner workings.

Our research establishes for the first time the relationship between the normal stem cell program and the cancer stem cell program, albeit in the context of the mammary gland, says Whitehead Institute Founding Member Robert Weinberg. There may be slight variations on this theme in other epithelial tissues, but at least the relationship is firmly secured in the context of the mammary gland, which seems to be a pretty good model for other epithelial tissues. Tumor-initiating cells are in fact cancer stem cells, but cancer stem cells do not arise from normal stem cells.

The Weinberg labs findings are described in this weeks issue of the journal Nature.

Previous work in the lab has demonstrated that cancer stem cells emerge after undergoing an epithelial-to-mesenchymal transition (EMT), which endows the cells with the motility and flexibility required for seeding new tumors. The EMT may also confer on the cells the ability to resist standard chemotherapeutics.

In the current line of research, Xin Ye, who is a senior research associate in the Weinberg lab and the lead author of the Nature paper, used a mouse model that shows which cells within the normal and cancerous mammary gland express the related master regulators Snail and Slug, both of which confer stem-like traits on mammary cells. Slug, for its part, is especially potent in inducing the mesenchymal cell traits that are associated with high-grade, aggressive carcinomas.

Ye determined that different cell types in distinct tissue layers within the mammary gland express and are influenced by these master regulators. Slug, which regulates gland-reconstituting activity in breast tissue, is expressed at higher levels in normal stem cells found in the basal layer of mammary ducts. Snail, a factor first discovered in the context fruit fly embryonic development, is expressed by tumor-initiating cells in the luminal layer of cells in these ducts. Snail has the power to confer aggressive traits on cancer cells that Slug is incapable of doing when it is expressed at normal levels.

Snail-positive cancer stem cells arise in a different population of cells than the cells that harbor normal stem cells, says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology and Director of the MIT/Ludwig Center for Molecular Oncology. Normal stem cells reside in one layer in the mammary duct; cancer stem cells arise in another. What that means is that cancer stem cells do not arise from normal stem cells. This has been a point of much discussion, but now there is evidencefinally!

Such basic insights about the source of cancer stem cells and the differences between normal and cancer cells could provide leads for new cancer therapeutics.

Were starting to realize that a lot of things are regulated differentially in normal versus cancer settings, says Ye. It doesnt even need to be cancer stem cell versus normal stem cellcancer versus normal is really different. If we understand the differences better, we have a better chance of treating this disease.

This work was supported by the National Research Foundation, Singapore (NRFNRFF2015-04), American Cancer Society, Ludwig Foundation, Breast Cancer Research Foundation, National Cancer Institute Program (P01-CA080111, U01-CA184897, R01-CA078461, K99-CA194160), Samuel Waxman Cancer Research Foundation, Mattina R. Proctor Foundation, Helen Hay Whitney Foundation, and Andria and Paul Heafy.

Written by Nicole Giese Rura

* * *

Robert Weinbergs primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Professor of Biology at Massachusetts Institute of Technology and Director of the MIT/Ludwig Center for Molecular Oncology.

* * *

Full Citation:

Distinct EMT programs control normal mammary stem cells and tumour-initiating cells

Nature, online September 2, 2015.

Xin Ye (1), Wai Leong Tam (1, 2, 3), Tsukasa Shibue (1), Yasemin Kaygusuz (1), Ferenc Reinhardt (1), Elinor Eaton (1), Robert A. Weinberg (1,4,5).

1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA

2. Genome Institute of Singapore, 60 Biopolis Street Singapore 138672, Singapore

3. Cancer Science Institute of Singapore, 14 Medical Drive, Singapore

4. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

5. Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

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Variations in cell programs control cancer and normal stem ...

Four Prentice students headed to the University of Wisconsin (UW)-Madison in mid-July for a camp geared at illuminating stem cell research and related technology for rural youth.

The local group, Hailey Enders, Carli Hora, Jesse Isaacson and Joseph Jast, joined 12 other students hailing from Tomah, Winter, and North Crawford in this unrivaled four-day experience known as the "Discovery Summer Science Camp.

Prentice School instructor Mike Dunbar said that the program, running from July 13 to July 16 gave students from our rural area the chance to see what real researchers in Madison are doing, and, because the students participated in many lab activities, helped them feel like part of the experience there.

Students got a chance to see research facilities defining the Wisconsin Institute for Discovery and other divisions of learning at UW-Madison, including the Chemistry Department. In addition, they got a firsthand look at technology used in the UW-Health Clinical Simulation Laboratory, set up at the UW- Hospital.

Their stops at research facilities brought students opportunities to run real tests used by practicing lab workers. Afterwards, students had the benefit of learning about the science underlying those hands-on activities with talks from active researchers in connected fields, according to Dunbar.

The technologies used there and the laboratory facilities provided a unique insight for these students into what is current and cutting edge, which most high school students anywhere would never get to see, Dunbar stated.

As one genuine lab task, young scientists had the opportunity to conduct live stem cell passaging, which consists of taking cultured stem cells and creating, or passaging, six entirely new cultures from the original cell material, according to Dunbar.

Via the discussion that surrounded this camp segment and the required readings students completed ahead of the camp, budding researchers learned about something known as induced pluripotent" stem cells, or IPS cells. Those cells are harvested from an adults skin and with lab manipulation, are returned to stem cell form, sparing researchers from needing to use the cells of embryos for research.

The possibilities for scientific gain with use of these cells are numerous as students found out from the talks given by researchers later in the camp, Dunbar stated.

Another session in the lab delivered a close-up look at the process of cryopreservation, made possible by the use of liquid nitrogen.

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Local students take part in stem cell camp | Local | apg ...

Heres a collection of recent headlines from Wisconsins innovation community:

Waukesha-based Elli Health has changed its name to Intellivisit and tacked nearly $400,000 on to a funding round that previously raised about $780,000, according to SEC filings. The companys software enables virtual doctor visits.

Madison-based Health eFilings raised $934,500 in a seed funding round that could reach $1.5 million, according to a new SEC filing. The company sells software that helps healthcare providers report care quality data as required by Medicare. The startup is led by Robert Hopton, whose previous company, Idle Free Systems, was acquired last year by Phillips & Temro Industries.

Madison-based Digsite raised $775,000 in a seed funding round, according to an SEC filing. The companys software provides private online forums for marketers, researchers, and digital agencies to interact with customers and share photos and videos from any device.

Aurora Health Care, the Milwaukee-based healthcare system serving eastern Wisconsin and northern Illinois, became a lead investor in StartUp Health, the New York-based company that invests in digital health startups and gives them access to mentors, industry connections, and business training services. The size of Auroras investment wasnt disclosed.

The Water Council received a $230,000 grant from JPMorgan Chase to continue providing specialized training for angel investors and programs to connect corporate innovation departments with water technology startups looking for investment capital. TheMilwaukee-based Water Council is in its second year of funding from a JPMorgan Chase small business funding program.

In other local water industry news, Milwaukee-based Rexnord (NYSE: RXN) announced its relocating the headquarters of its Zurn subsidiary from Pennsylvania to the Reed Street Yards near downtown Milwaukee, where a new water technology business park is being built next to The Water Councils Global Water Center. Zurn makes toilets, sinks, and a variety of other plumbing-related products.

Monona-based Shine Medical Technologies said it was awarded a $150,000 Phase 1 Small Business Innovation Research grant from the National Science Foundation. The money will go toward development of a process for extracting and purifying iodine-131, a type of medical isotope used in treating Graves disease and cancer, the company said. This is a potential product Shine could manufacture when it opens a facility in Janesville in a few years.

The primary material Shine has said it intends to produceat Janesville, though, is molybdenum-99, which then decays into technetium-99, the most common medical isotope injected into patients for medical scans to diagnose things like cancer and heart disease.

Madison-based WiCell, the nonprofit that provides stem cell banking and testing services, has been chosen to store and distribute the induced pluripotent stem cell lines from more than 1,500 donors as part of a five-year, $80 million program funded by the National Heart, Lung, and Blood Institute. The initiativedubbed Next Generation Genetic Association Studiesis investigating genetic variations in humans to learn more about diseases. Participating researchers hail from across the U.S., including the Medical College of Wisconsin, Boston University, Harvard University, Stanford University, UC-San Diego, and Scripps Research Institute.

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Wisconsin Roundup: VC Funding, StartUp Health, Stem Cells ...

The news that legendary Green Bay Packer quarterback Bart Starr has undergone stem cell therapy to recover from a stroke has raised the profile for a promising but unproven regenerative treatment intended to replace dead neurons with live ones.

The University of Wisconsin-Madison's Su-Chun Zhang was the first scientist to isolate neural stem cells from embryonic stem cells and then from other types of all-purpose stem cells. He says medical researchers and the federal government have a responsibility to forge ahead with clinical trials to prove whether and how these flexible cells can replace damaged or dead neural cells caused by spinal cord injury, stroke and Lou Gehrig's disease (ALS).

"We have no effective treatment for stroke," says Zhang, a medical doctor and Ph.D. researcher at the UW's Waisman Center. "After a couple of hours, the cells are dead if they don't have a blood supply. And the brain has a very limited capacity to regenerate, particularly in older patients."

Embryonic stem cells the cells that give rise to all body tissues were first cultured by James Thomson at UW-Madison in 1998. Just three years later in 2001 Zhang discovered how to grow neural cells from embryonic stem cells.

Since then, he has been instrumental in differentiating these neural cells into neurons, which carry nerve signals, and glial cells, which keep neurons healthy. UW-Madison currently has more than 90 faculty working on the basic science and regenerative potential of stem cells. UW scientists publish more than 500 research articles each year on stem cells.

Zhang expressed hope that Starr will recover, but says there are plenty of question marks, such as what type of cells were used, and how they were inserted into the body.

In a statement Wednesday, Starr's family announced he was participating in a stem-cell trial but gave no details of how or where he was being treated. Published reports have said that the family received information about stem-cell treatment in Tijuana, Mexico, undergone by hockey Hall-of-Famer Gordie Howe.

Given the lack of available therapies for stroke in the U.S., treatments and trials outside the country can understandably appeal to patients and families searching for help.

But Zhang says there are questions about whether foreign trials meaningfully advance the science of the field. Curious about the widespread clinical trials for stem cell therapy said to be underway, he says he "went through lists of thousands of clinical trials, mostly in foreign countries, looking for the outcomes, and I hardly saw any posted results." Patients usually disappear after returning home, he says, "and many of these so-called trials are not really trials, where you follow the patient and set up standards to measure the outcome. What do they teach you?"

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Stem cell expert: Bart Starr treatment shows need for ...

When you buy a replacement alternator for your 88 Toyota Corolla, its easy enough to see the new part. The same cannot always be said for the replacement cells that are being tested for healing or replacing diseased tissue. These cells, derived from various kinds of stem cells, have great healing potential, but as they enter clinical trials, scientists need better ways to identify the transplanted cellsand the daughter cells they spawn.

In a lab at the Wisconsin Institutes for Medical Research, PhD student Christina Lewis examines an MRI scan of a rat brain to determine how quickly a specific contrast agent gets distributed throughout the organ. Her findings will establish a baseline for future tests involving stem cells transplants. (Photo: Nik Hawkins)

Cell therapies are beginning to be tested in clinics, and we need a way to explain why we see the results we see, says Christina Lewis, a PhD student in the lab of Masatoshi Suzuki, assistant professor of comparative biosciences at the UW School of Veterinary Medicine.

For example, neural cells grown from stem cells are being tested to treat ALS, the fatal nerve-muscle disorder sometimes called Lou Gehrigs disease, Lewis says. If we dont see an improvement, we need to understand what went wrong. Did the cells die? Did they migrate somewhere else?

And if the patient does improve, knowing that the transplanted cells are present and alive helps document that the treatment works.

Lewis, Suzuki, and colleague Stephen Graves, a research assistant in the UW-Madison Department of Medical Physics, have tested a solution to the problem in the form of a gene in the stem cells that picks up a manganese isotope that can be seen by both PET (positron emission tomography) and MRI (magnetic resonance imaging) scanners. The isotope serves as a beacon for the transplanted cells, revealing their location in the body.

PET and MRI are both useful, says Lewis, and this combination gives us flexibility, depending on what is available in the clinic. MRI gives great soft-tissue contrast and good detail and shows the surrounding anatomy. PET can detect a very small amount of the manganese contrast agent so we can reduce the dose of the agent.

Finally, because the detection rests on a genetic alteration of the stem cell, subsequent generations of cells can also be seen, says Suzuki, an expert in neural stem cells. We can potentially monitor cell survival and behavior for months or even years.

The new technique would need approval from the Food and Drug Administration before entering human clinical trials.

Lewis and Suzuki published the results of their study in the journal Theranostics. Other collaborators include medical physics professors M. Elizabeth Meyer and Robert Nickles.

Excerpt from:
Study Reveals How Imaging Technology Can Track Stem Cell ...

Visit the webpage of the Stem Cell Action Coalition for national legislative updates.

The following summary is provided by Wisconsin Stem Cell Now:

A. Is embryonic stem cell research eligible for federal funding?

The National Institutes of Health (NIH) funds research using adult stem cells, embryonic stem cells, stem cells obtained from umbilical cord blood, and stem cells derived from non-human tissue.

The policy of the Bush administration was to limit the use of federal dollars to research using embryonic stem cell lines created prior to August 9, 2001. While at the time of this decision President Bush claimed that approximately 64 stem cell lines would be eligible for federal funding, it soon became apparent that far fewer stem cell lines were actually viable and available to researchers. During the Bush Administration, 21 stem cell lines derived from human embryos were available to researchers who wished to obtain federal funding of their work.

The National Stem Cell Bank was formed as the national repository of these embryonic stem cell lines (and also three iPS stem cell lines). Established by WiCell, a private, not-for-profit supporting organization to the University of Wisconsin-Madison, the National Stem Cell Bank is funded through a federal grant.

Meanwhile, during the Bush Administration, researchers were continuing to produce hundreds if not thousands of new embryonic stem cell lines after August 9, 2001. In most cases, these post-2001 stem cell lines were derived with embryos that were created during the process of in vitro fertilization and that were subsequently donated to researchers in lieu of destruction. As laboratory techniques improved after 2001, and as researchers learned more about cell biology, the quality of these newer embryonic stem cell lines exceeded the quality of the lines created earlier.

During the Bush Administration, Congress twice passed legislation seeking to extend federal funding to these post-2001 embryonic stem cell lines. In both cases, President Bush vetoed the bill and supporters failed to override the veto.

Therefore, the Bush era restrictions on federal funding for embryonic stem cell research placed significant limits on researchers. The embryonic stem cell lines eligible to receive federal funding were of a lesser quality, and are therefore less useful to researchers. Research institutions that wished to conduct research using both pre-2001 and post-2001 embryonic stem cell lines had to either set up elaborate accounting systems or else construct completely separate facilities in order to assure that no federal dollars were indirectly used to support research outside of National Institutes of Health (NIH) guidelines. In addition, collaboration between institutions, which often leads to faster progress, became more difficult because different funding rules applied to different institutions.

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Wisconsin Stem Cell Now Issues and Legislation

Madison, Wisconsin - In 2009, a group of cardiovascular researchers at the University of Wisconsin School of Medicine and Public Health proved that functional human heart muscle cells can be produced from genetically reprogrammed skin cells.

According to the American Heart Association (AHA), the discovery was one of the10 most important research advances for cardiovascular disease and stroke for the year.

Timothy Kamp, MD, PhD, FACC,a UW professor of medicine, in collaboration with stem cell pioneer James Thomson, DVM, PhD,led the team that demonstrated that human induced pluripotent stem (IPS) cells could be differentiated into contracting cardiac cells. The team's findings raise the possibility that a patient's own skin cells could someday be used to repair damaged heart tissue.

"It's certainly an honor to have our research recognized by an organization devoted to the same goal we are-keeping patients' hearts healthy," says Dr. Kamp. "Much more research is needed before this type of stem cell can be used clinically, but there is significant promise that these cells may provide a powerful new treatment for heart failure and other degenerative diseases of the heart."

The AmericanHeart Associationdoesn't assign rank to the research advances on its annual list. Other notable advances included studies documenting the effectiveness of controlling calories in maintaining heart health, the effectiveness of oral blood thinners in patients with stroke and atrial fibrillation and the impact of smoke-free legislation on reducing heart attacks.

Date Published: 01/22/2010

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UW-Madison Heart Stem Cell Study Among American Heart ...

January 17, 2008

Tags: Lodish LabProtein Function

CAMBRIDGE, Mass. Patients with leukemia, certain autoimmune diseases and genetic defects such as sickle-cell anemia can be treated with blood stem cells either from a donors bone marrow or from cord bloodbut the supply of effective stem cells often runs short.

Now, researchers in the lab of Whitehead Member Harvey Lodish have found a way to multiply in culture adult hematopoietic (blood- forming) stem cells from human cord blood 20-fold, a major milestone that offers promise for bone marrow transplants and perhaps even gene therapy. Cord blood can be easily collected and stored as a frozen product, making it readily available.

Human cord blood is a rich source of stem cells, but offers too few of those cells to transplant into an adult, says Lodish. Previously we identified five growth factors that acting together in culture expanded mouse bone marrow hematopoietic stem cells 30-fold. Building on this research weve now identified five growth factors needed to stimulate human cord blood stem cells to divide in culture and make 20-fold as many stem cells. The paper was pre-published online in Blood on January 17, 2008.

Two novel growth factors (angiopoietin-like 5 and IGFBP2) work in combination with three previously identified growth hormones (SCF (Stem Cell Factor), TPO (Thrombopoietin) and Flt3 ligand to stimulate the growth of these stem cells.

Known as hematopoietic stem cells, the cells give rise to oxygen-carrying red blood cells, white blood cells, and all of the cells that comprise the immune system. Previous efforts to grow human hematopoietic stem cells in culture have proven extraordinarily difficult because they rapidly differentiate into mature blood or immune cells.

Our finding builds on previous work studying hematopoietic cells in which we discovered a novel cell population that when cultured in a dish with stem cells enabled them to multiply, says Chengcheng Zhang, first author of the paper, formerly a postdoctoral researcher in the Lodish lab and now an assistant professor of physiology and developmental biology at the University of Texas Southwestern Medical Center in Dallas. We searched for genes that were active in these and other stem cell supportive cells, and identified genes that encoded growth factors. We then added the growth factors to the isolated hematopoietic stem cells and increased the number of stem cells in culture.

To make sure that these were still viable stem cells, the researchers transplanted them into immune-deficient mice, and measured the resulting population of various sorts of human blood and immune system cells successfully growing in the mice.

The researchers note that this finding may also lead to advances in gene therapy, in which a genetic defect would be corrected by administering a healthy version of the gene into a patient. During gene therapy, hematopoietic stem cells from a patient would be isolated and exposed to a harmless virus that expresses a correct version of the mutated gene, and then the stem cells would be transferred back into the patient.

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Whitehead Institute - News - 2008 - Human blood stem cells ...