Category Archives: Stem Cell Medical Center


Skin layer grown from human stem cells could replace animals in drug and cosmetics testing

PUBLIC RELEASE DATE:

24-Apr-2014

Contact: Jenny Gimpel jenny.gimpel@kcl.ac.uk 44-020-784-84334 King's College London

An international team led by King's College London and the San Francisco Veteran Affairs Medical Center (SFVAMC) has developed the first lab-grown epidermis the outermost skin layer - with a functional permeability barrier akin to real skin. The new epidermis, grown from human pluripotent stem cells, offers a cost-effective alternative lab model for testing drugs and cosmetics, and could also help to develop new therapies for rare and common skin disorders.

The epidermis, the outermost layer of human skin, forms a protective interface between the body and its external environment, preventing water from escaping and microbes and toxins from entering. Tissue engineers have been unable to grow epidermis with the functional barrier needed for drug testing, and have been further limited in producing an in vitro (lab) model for large-scale drug screening by the number of cells that can be grown from a single skin biopsy sample.

The new study, published in the journal Stem Cell Reports, describes the use of human induced pluripotent stem cells (iPSC) to produce an unlimited supply of pure keratinocytes the predominant cell type in the outermost layer of skin - that closely match keratinocytes generated from human embryonic stem cells (hESC) and primary keratinocytes from skin biopsies. These keratinocytes were then used to manufacture 3D epidermal equivalents in a high-to-low humidity environment to build a functional permeability barrier, which is essential in protecting the body from losing moisture, and preventing the entry of chemicals, toxins and microbes.

A comparison of epidermal equivalents generated from iPSC, hESC and primary human keratinocytes (skin cells) from skin biopsies showed no significant difference in their structural or functional properties compared with the outermost layer of normal human skin.

Dr Theodora Mauro, leader of the SFVAMC team, says: "The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skin's barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

Dr Dusko Ilic, leader of the team at King's College London, says: "Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics. Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, and could thus be tailored to study a range of skin conditions and sensitivities in different populations."

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Skin layer grown from human stem cells could replace animals in drug and cosmetics testing

PARKINSONS ASSOCIATION HIRES STEM CELL SCIENTIST

The Parkinsons Association has hired its inaugural scientist, a step the San Diego-based patient advocacy group describes as its first toward becoming a research center.

The scientist, Andrs Bratt-Leal, helps lead a project called Summit4StemCell.org, which aims to treat eight local Parkinsons patients with new brain cells grown from their own skin. The patients are raising money for their treatment. Theyre assisted by the nonprofit association and partners Scripps Health and The Scripps Research Institute.

If all goes well, treatment will start early next year.

Bratt-Leal continues to work in the lab of stem cell expert Jeanne Loring, head of the Center for Regenerative Medicine at The Scripps Research Institute. The medical arm of the project is being directed by Dr. Melissa Houser, a Scripps Health neurologist.

Bratt-Leal, as it turns out, has been working on a project of his own: Hes an expectant father. Bratt-Leal had considered leaving his job in Lorings lab to seek work closer to home in San Clemente.

Jeanne asked me to see if we could negotiate a contract with him where he would be able to stay in a broader capacity, said Jerry Henberger, the associations executive director. He didnt have the ability through The Scripps Research Institute to take that next step.

The association found the money to hire Bratt-Leal, who started as its senior scientist in February. As part of the deal, he continues to work under Lorings direction.

Raising money has been a constant concern since Summit4StemCell was founded in 2011. If a clinical trial of the therapy is approved, millions will be needed to pay for the treatment and kept as a reserve for care if the therapy goes awry.

The good news is that funding may be available from the states stem cell agency, the California Institute for Regenerative Medicine, Henberger said. The group plans to submit a proposal when the next funding round begins.

In addition, the project may qualify for financial backing from the Sanford Stem Cell Clinical Center, which was established in November with a $100 million gift from philanthropist T. Denny Sanford. The center integrates operations at UC San Diego and other La Jolla research centers to turn the science into therapies.

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PARKINSONS ASSOCIATION HIRES STEM CELL SCIENTIST

Human Stem Cells Converted to Functional Lung Cells …

NEW YORK, NY For the first time, scientists have succeeded in transforming human stem cells into functional lung and airway cells. The advance, reported by Columbia University Medical Center (CUMC) researchers, has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study was published today in the journal Nature Biotechnology.

Human embryonic stem cells differentiated into type II alveolar lung epithelial cells (green). A large portion of these transformed cells express surfactant protein B (red), which indicates that they are functional type II cells. Image credit: Sarah Xuelian Huang, PhD at the Columbia Center for Translational Immunology at CUMC.

Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine, said study leader Hans-Willem Snoeck, MD, PhD, professor of medicine (in microbiology & immunology) and affiliated with the Columbia Center for Translational Immunology and the Columbia Stem Cell Initiative. Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplantsthat is, transplants that use a patients own skin cells to generate functional lung tissue.

The research builds on Dr. Snoecks 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endodermprecursors of lung and airway cells. (Human iPS cells closely resemble human ES cells but are generated from skin cells, by coaxing them into taking a developmental step backwards. Human iPS cells can then be stimulated to differentiate into specialized cellsoffering researchers an alternative to human ES cells.)

In the current study, Dr. Snoeck and his colleagues found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells (cells that cover the lung surface). The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

The findings have implications for the study of a number of lung diseases, including idiopathic pulmonary fibrosis (IPF), in which type 2 alveolar epithelial cells are thought to play a central role. No one knows what causes the disease, and theres no way to treat it, says Dr. Snoeck. Using this technology, researchers will finally be able to create laboratory models of IPF, study the disease at the molecular level, and screen drugs for possible treatments or cures.

In the longer term, we hope to use this technology to make an autologous lung graft, Dr. Snoeck said. This would entail taking a lung from a donor; removing all the lung cells, leaving only the lung scaffold; and seeding the scaffold with new lung cells derived from the patient. In this way, rejection problems could be avoided. Dr. Snoeck is investigating this approach in collaboration with researchers in the Columbia University Department of Biomedical Engineering.

I am excited about thiscollaboration with Hans Snoeck, integrating stem cell science withbioengineering in the search for new treatments for lung disease, said Gordana Vunjak-Novakovic, PhD, co-author of the paper and Mikati Foundation Professor of Biomedical Engineering at Columbias Engineering School and professor of medical sciences at Columbia University College of Physicians and Surgeons.

The paper is titled, Highly efficient generation of airway and lung epithelial cells from human pluripotent stem cells.

The other contributors are Sarah X.L. Huang, Mohammad Naimul Islam, John ONeill, Zheng Hu, Yong-Guang Yang, Ya-Wen Chen, Melanie Mumau, Michael D. Green, and Jahar Bhattacharya (all at CUMC).

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Cloning advance means human tissues could be regrown, even in old age

The advance could lead to tissue-transplant operations for a range of debilitating disorders, such as Parkinson's disease, multiple sclerosis, heart disease and spinal cord injuries.

Last year, a team created stem cells from the skin cells of babies, but it was unclear whether it would work in adults.

However, a team of scientists from the Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles and the University of Seoul said they had achieved the same result with two men, one aged 35, the other the 75-year-old. "The proportion of diseases you can treat with lab-made tissue increases with age. So if you can't do this with adult cells it is of limited value," said Robert Lanza, co-author of the research, which was published in the journal Cell Stem Cell.

The technique works by removing the nucleus from an unfertilised egg and replacing it with the nucleus of a skin cell. An electric shock causes the cells to divide until they form a "blastocyst", a small ball of a few hundred cells.

In IVF, a blastocyst is implanted into the womb, but with the new technique the cells would be harvested to create other organs or tissues.

The breakthrough is likely to reignite the debate about the ethics of creating human embryos for medical purposes and the possible use of the same technique to produce cloned babies - which is illegal in Britain.

Although the embryos created may not produce a human clone even if implanted in a womb, the prospect is now closer. However, scientists have tried for years to clone monkeys and have yet to succeed.

Dr Lanza admitted that without strong regulations, the early embryos produced in therapeutic cloning "could also be used for human reproductive cloning, although this would be unsafe and grossly unethical". However, he said it was important for the future of regenerative medicine that research into therapeutic cloning should continue.

Shoukhrat Mitalipov, a reproductive biologist from Oregon Health and Science University, who developed the technique last year, said: "The advance here is showing that [nuclear transfer] looks like it will work with people of all ages.

"I'm happy to hear that our experiment was verified and shown to be genuine."

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Cloning advance means human tissues could be regrown, even in old age

Stanford scientists identify source of most cases of invasive bladder cancer

PUBLIC RELEASE DATE:

20-Apr-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. A single type of cell in the lining of the bladder is responsible for most cases of invasive bladder cancer, according to researchers at the Stanford University School of Medicine.

Their study, conducted in mice, is the first to pinpoint the normal cell type that can give rise to invasive bladder cancers. It's also the first to show that most bladder cancers and their associated precancerous lesions arise from just one cell, and explains why many human bladder cancers recur after therapy.

"We've learned that, at an intermediate stage during cancer progression, a single cancer stem cell and its progeny can quickly and completely replace the entire bladder lining," said Philip Beachy, PhD, professor of biochemistry and of developmental biology. "All of these cells have already taken several steps along the path to becoming an aggressive tumor. Thus, even when invasive carcinomas are successfully removed through surgery, this corrupted lining remains in place and has a high probability of progression."

Although the cancer stem cells, and the precancerous lesions they form in the bladder lining, universally express an important signaling protein called sonic hedgehog, the cells of subsequent invasive cancers invariably do not a critical switch that appears vital for invasion and metastasis. This switch may explain certain confusing aspects of previous studies on the cellular origins of bladder cancer in humans. It also pinpoints a possible weak link in cancer progression that could be targeted by therapies.

"This could be a game changer in terms of therapeutic and diagnostic approaches," said Michael Hsieh, MD, PhD, assistant professor of urology and a co-author of the study. "Until now, it's not been clear whether bladder cancers arise as the result of cancerous mutations in many cells in the bladder lining as the result of ongoing exposure to toxins excreted in the urine, or if it's due instead to a defect in one cell or cell type. If we can better understand how bladder cancers begin and progress, we may be able to target the cancer stem cell, or to find molecular markers to enable earlier diagnosis and disease monitoring."

Beachy is the senior author of the study, which will be published online April 20 in Nature Cell Biology. He is the Ernest and Amelia Gallo Professor in the School of Medicine and a member of the Stanford Cancer Institute and the Stanford Institute for Stem Cell Biology and Regenerative Medicine. He is also a Howard Hughes Medical Institute investigator. Kunyoo Shin, PhD, an instructor at the institute, is the lead author.

Bladder cancer is the fourth most common cancer in men and the ninth most common in women. Smoking is a significant risk factor. There are two main types of the disease: one that invades the muscle around the bladder and metastasizes to other organs, and another that remains confined to the bladder lining. Unlike the more-treatable, noninvasive cancer which comprises about 70 percent of bladder cancers the invasive form is largely incurable. It is expensive and difficult to treat, and the high likelihood of recurrence requires ongoing monitoring after treatment.

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Stanford scientists identify source of most cases of invasive bladder cancer

Umbilical cord blood transplants become standard

Sarah and Marc discovered that in the Philadelphia area, even if parents realized umbilical cords were more than just waste products of childbirth, there was no easy way to donate the tissue. So they established the Mason Shaffer Foundation to change that.

This month, Temple University Hospital launched a program in collaboration with the foundation and the New Jersey Cord Blood Bank to educate expectant parents and enable them to donate in a convenient way - at no charge to them or Temple. The foundation provides the educational material, and the cord-blood bank covers the collection costs, which are offset by health insurance reimbursement for transplants.

Three years ago, Lankenau Medical Center in Wynnewood became the foundation's first cord-blood donation center.

Temple, however, is expected to help fill the desperate need for a more racially diverse cord-blood stockpile. That need was recognized by the federal Stem Cell Therapeutic and Research Act of 2005, which included funding that will help underwrite the first year of Temple's program.

Of the 3,200 babies delivered at Temple each year, 65 percent are African American, and 30 percent are Hispanic.

"Ethnically diverse groups are underrepresented as cord-blood donors and have a lower chance of finding a matched donor," said Dimitrios Mastrogiannis, Temple's director of maternal fetal medicine.

"Our biggest challenge is building diversity," echoed Roger Mrowiec, scientific director of Community Blood Services in Montvale, N.J., which runs the New Jersey Cord Blood Bank. "A Caucasian has about a 95 percent chance of finding a match. For Hispanics, that falls to 70 percent, and for African Americans, it's only 60 percent."

Mrowiec spoke at a Temple news conference where the grown-ups were happily upstaged by the foundation's eponymous poster boy. Although Mason is small for his age and blind in his left eye, his transplant cured his disease: malignant infantile osteopetrosis.

"Do you know why we're here?" his mother asked him.

"Because I got cells that fixed my bones," the precocious preschooler piped up.

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Umbilical cord blood transplants become standard

Scientists use cloning to make stem cells matched to two adults

Scientists have replicated one of the most significant accomplishments in stem cell research by creating human embryos that were clones of two men.

The lab-engineered embryos were harvested within days and used to create lines of infinitely reproducing embryonic stem cells, which are capable of growing into any type of human tissue.

The work, reported Thursday in the journal Cell Stem Cell, comes 11 months after researchers in Oregon said they had produced the world's first human embryo clones and used them to make stem cells. Their study, published in Cell, aroused skepticism after critics pointed out multiple errors and duplicated images.

In addition, the entire effort to clone human embryos and then dismantle them in the name of science troubles some people on moral grounds.

MORE: Medicines and machines, inspired by nature

The scientists in Oregon and the authors of the new report acknowledged that the clones they created could develop into babies if implanted in surrogate wombs. But like others in the field, they have said reproductive cloning would be unethical and irresponsible.

The process used to create cloned embryos is called somatic cell nuclear transfer, or SCNT. It involves removing the nucleus from an egg cell and replacing it with a nucleus from a cell of the person to be cloned. The same method was used to create Dolly the sheep in 1996, along with numerous animals from other species.

Human cloning was a particular challenge, in part because scientists had trouble getting enough donor eggs to carry out their experiments. Some scientists said SCNT in humans would be impossible.

Dr. Robert Lanza, the chief scientific officer for Advanced Cell Technology Inc. in Marlborough, Mass., has been working on SCNT off and on for about 15 years. He and his colleagues finally achieved success with a modified version of the recipe used by the Oregon team and skin cells donated by two men who were 35 and 75.

After swapping out the nucleus in the egg cell, both groups used caffeine to delay the onset of cell division a technique that has been called "the Starbucks effect." But instead of waiting 30 minutes to prompt cell division, as was done in the Oregon experiment, Lanza and his team waited two hours.

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Scientists use cloning to make stem cells matched to two adults

Researchers successfully clone adult human stem cells

20 hours ago by Bob Yirka Credit: Cell Stem Cell, DOI: 10.1016/j.stem.2014.03.015

(Phys.org) An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem cells. A paper by the team describing their work has been published in the journal Cell Stem Cell.

The achievement by the team is actually a replication of work done by another team just last yearin that effort the team did the same thing but used donor cells from infants. In this new experiment, two men aged 35 and 75 donated skin cells.

Technically called somatic-cell nuclear transfer aka "therapeutic cloning" the process is similar to that used to clone Dolly the sheep back in 1997. Since that time, researchers have run into a myriad of obstacles in achieving the same results in humans, though it should be noted that there is a major difference in objectivewith humans, the aim is to clone stem cells so that they can be used to treat diseases, not reproduce whole human beings.

To clone the stem cells, the researchers used unfertilized eggs donated by several unidentified women. After removing the DNA material inside the egg, new DNA material extracted from the skin cells of the male donors was injected inside and the resulting filled egg was exposed to a small dose of electricity to cause fusingthe egg was then allowed to "rest" for two hours. Afterwards each egg reprogrammed itself and grew into a blastocyst which eventually grew into a pluripotent stem cell that genetically matched the skin donor. Theoretically such stem cells could then be engineered to grow into various cells, e.g. heart, lung, liver, for transplant into a patient.

Funding for the research was provided by an unnamed foundation and the Korean Governmentthe experiments were conducted in a lab in California. The researchers point out that the process cannot be used to create a whole human being.

The team notes that despite their success, there is still a lot of work to do before cloned stem cells become a viable option for treating medical problems in people. They note that out of 77 eggs donated and used in the experiments, only two led to successful cloningone from each of the male donors. Their experiments do prove however, they add, that successful cloning of human stem cells is possible with donors of any age.

Explore further: Researchers discover ancient virus DNA remnants necessary for pluripotency in humans

More information: Human Somatic Cell Nuclear Transfer Using Adult Cells, Cell Stem Cell, dx.doi.org/10.1016/j.stem.2014.03.015

Summary Derivation of patient-specific human pluripotent stem cells via somatic cell nuclear transfer (SCNT) has the potential for applications in a range of therapeutic contexts. However, successful SCNT with human cells has proved challenging to achieve, and thus far has only been reported with fetal or infant somatic cells. In this study, we describe the application of a recently developed methodology for the generation of human ESCs via SCNT using dermal fibroblasts from 35- and 75-year-old males. Our study therefore demonstrates the applicability of SCNT for adult human cells and supports further investigation of SCNT as a strategy for regenerative medicine.

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Researchers successfully clone adult human stem cells

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Stem Cell Therapy treatment for Rhinophyma in Ottawa Illinois

Results are a leap for embryonic stem cells

Scientists have replicated one of the most significant accomplishments in stem cell research by creating human embryos that were clones of two men.

The lab-engineered embryos were harvested within days and used to create lines of infinitely reproducing embryonic stem cells, which are capable of growing into any type of human tissue.

The work, reported Thursday in the journal Cell Stem Cell, comes 11 months after researchers in Oregon said they had produced the world's first human embryo clones and used them to make stem cells. Their study, published in Cell, aroused skepticism after critics pointed out multiple errors and duplicated images.

In addition, the entire effort to clone human embryos and then dismantle them in the name of science troubles some people on moral grounds.

The scientists in Oregon and the authors of the new report acknowledged that the clones they created could develop into babies if implanted in surrogate wombs. But like others in the field, they have said reproductive cloning would be unethical and irresponsible.

The process used to create cloned embryos is called somatic cell nuclear transfer, or SCNT. It involves removing the nucleus from an egg cell and replacing it with a nucleus from a cell of the person to be cloned. The same method was used to create Dolly the sheep in 1996, along with numerous animals from other species.

Human cloning was a particular challenge, in part because scientists had trouble getting enough donor eggs to carry out their experiments. Some scientists said SCNT in humans would be impossible.

Dr. Robert Lanza, the chief scientific officer for Advanced Cell Technology Inc. in Marlborough, Mass., has been working on SCNT off and on for about 15 years. He and his colleagues finally achieved success with a modified version of the recipe used by the Oregon team and skin cells donated by two men who were 35 and 75.

After swapping out the nucleus in the egg cell, both groups used caffeine to delay the onset of cell division a technique that has been called "the Starbucks effect." But instead of waiting 30 minutes to prompt cell division, as was done in the Oregon experiment, Lanza and his team waited two hours.

It remains unclear exactly how the egg causes the cells in previously mature tissues in this case, skin to transform into a more versatile, pluripotent state.

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Results are a leap for embryonic stem cells