'Genome editing' could correct genetic mutations for future generations

By adminDecember 16, 2014Stem Cell Medical Center

Scientists at Indiana University and colleagues at Stanford and the University of Texas have demonstrated a technique for "editing" the genome in sperm-producing adult stem cells, a result with powerful potential for basic research and for gene therapy.

The researchers completed a "proof of concept" experiment in which they created a break in the DNA strands of a mutant gene in mouse cells, then repaired the DNA through a process called homologous recombination, replacing flawed segments with correct ones.

The study involved spermatogonial stem cells, which are the foundation for the production of sperm and are the only adult stem cells that contribute genetic information to the next generation. Repairing flaws in the cells could thus prevent mutations from being passed to future generations.

"We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated," said Christina Dann, associate scientist in the Department of Chemistry at IU Bloomington and a co-author of the study. "This technique corrects the mutation, theoretically leaving no other mark on the genome."

The paper, "Genome Editing in Mouse Spermatogonial Stem/Progenitor Cells Using Engineered Nucleases," was published in the online science journal PLOS-ONE.

The lead author, Danielle Fanslow, carried out the research as an IU research associate and is now a doctoral student at Northwestern University. Additional co-authors are from the Stanford School of Medicine and the University of Texas Southwestern Medical Center.

A challenge to the research was the fact that spermatogonial stem cells, like many types of adult stem cells, are notoriously difficult to isolate, culture and work with. It took years of intensive effort by multiple laboratories before conditions were created a decade ago to maintain and propagate the cells.

For the IU research, a primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material. The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.

Stem cells that had been modified in the lab were then transplanted into the testes of sterile mice. The transplanted cells grew or colonized within the mouse testes, indicating the stem cells were viable. However, attempts to breed the mice were not successful.

"Whether the failure to produce sperm was a result of abnormalities in the transplanted cells or the recipient testes was unclear," the researchers write.

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'Genome editing' could correct genetic mutations for future generations

Baby cells learn to communicate using the lsd1 gene

By adminDecember 16, 2014Stem Cell Medical Center

21 hours ago Fruit fly ovarian follicle progenitor cells, with different colors marking a specific kind of activity (red) specific gene expression (green) and nuclear DNA (blue). Credit: Ming-Chia Lee and Allan Spradling

We would not expect a baby to join a team or participate in social situations that require sophisticated communication. Yet, most developmental biologists have assumed that young cells, only recently born from stem cells and known as "progenitors," are already competent at inter-communication with other cells.

New research from Carnegie's Allan Spradling and postdoctoral fellow Ming-Chia Lee shows that infant cells have to go through a developmental process that involves specific genes before they can take part in the group interactions that underlie normal cellular development and keep our tissues functioning smoothly. The existence of a childhood state where cells cannot communicate fully has potentially important implications for our understanding of how gene activity on chromosomes changes both during normal development and in cancerous cells. The work is published in Genes and Development.

The way that the molecules that package a cell's chromosomes are organized in order to control gene activity is known as the cell's "epigenetic state." The epigenetic state is fundamental to understanding Spradling and Lee's findings. To developmental biologists, changes in this epigenetic state ultimately explain how the cell's properties are altered during tissue maturation.

"In short, acquired epigenetic changes in a developing cell are reminiscent of the learned changes the brain undergoes during childhood," Spradling explained. "Just as it remains difficult to map exactly what happens in a child's brain as it learns, it is still very difficult to accurately measure epigenetic changes during cellular development. Not enough cells can usually be obtained that are at precisely the same stage for scientists to map specific molecules at specific chromosomal locations."

Lee and Spradling took advantage of the unsurpassed genetic tools available in the fruit fly to overcome these obstacles and provide new insight into the epigenetics of cellular development.

Using a variety of tools and techniques, they focused on cells in the fruit fly ovary and were able identify a specific gene called lsd1 that is needed for ovarian follicle progenitor cells to mature at their normal rate. The researchers found that the amount of the protein that is encoded by this gene, Lsd1, which is present in follicle progenitors decreases as the cells approach differentiation. What's more, the onset of differentiation could be shifted by changing the levels of Lsd1 protein that are present. They deduced that differentiation ensues when Lsd1 levels fall below a critical threshold, and that this likely corresponds to when genes can be stably expressed.

"The timing of differentiation is very important for normal development," Lee said. "Differentiation onset determines how many times progenitors divide, and even small perturbations in Lsd1 levels changed the number of follicle cells that were ultimately produced, which reduced ovarian function."

Previously, it was thought that the follicle cell progenitors started to differentiate based on an external signal they received from another kind of ovarian cells known as germ cells. Lee and Spradling found that while this germ cell signal was essential, it was already being regularly sent even before the progenitors responded. Instead, it was the Lsd1-mediated change in their epigenetic state that timed when progenitor cells started to respond to the signal and begun differentiating. Once they become competent, however, differentiating follicle cells communicate extensively with their neighbors, and continued to do so throughout their lives.

As is frequently the case in basic biological research, the molecules and mechanisms studied here are found in most multicellular animals and hence the researchers conclusions are likely to apply broadly throughout the animal kingdom, including in humans.

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Baby cells learn to communicate using the lsd1 gene

Canadian scientists crack stem cell reprogramming code

By adminDecember 11, 2014Stem Cell Medical Center

By Sheryl Ubelacker The Canadian Press

WATCH: Dr. Andras Nagy describes the scientific breakthrough he led in solving the mystery of the stem cell reprogramming code.

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

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Canadian scientists crack stem cell reprogramming code

NYSCF and the CMTA enter collaboration to advance neuropathies research

By adminDecember 11, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

10-Dec-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation @nyscf

New York, NY (December 10, 2014) - The New York Stem Cell Foundation (NYSCF) Research Institute, a non-profit organization dedicated to accelerating cures through stem cell research, announced a collaboration today with the Charcot-Marie-Tooth Association (CMTA), a patient-led disease foundation with the mission to advance research on genetic neuropathies that leads to the development of new therapies. The immediate aim of the collaboration is to develop a bank of induced pluripotent stem cell (iPSC) lines for a variety of neuropathy disorders of known genetic causation and to eventually develop personalized drug therapies.

NYSCF will make stem cells lines from Charcot-Marie-Tooth patient materials that have been curated in a biobank assembled by Dr. Michael Shy at the University of Iowa, a member of the CMTA STAR consortium of sponsored investigators. Utilizing its automated technology, the NYSCF Global Stem Cell ArrayTM, NYSCF will systematically generate iPSC lines from tissue samples obtained from patients representing a number of disease states. These cell lines will then be used to develop methods for creating differentiated cells that mimic the myelin-producing Schwann cells that are defective in Type 1 Charcot-Marie-Tooth (CMT) disorders of peripheral nerve, as well as the motor and sensory neurons that are defective in Type 2 disorders. Members of the STAR consortium currently engaged in this CMTA-sponsored effort to differentiate iPSC lines include Dr. Robert Baloh, Cedar-Sinai Medical Center, and Dr. Gabsang Lee, Johns Hopkins University. The ultimate aim of this research is to create a personalized medicine approach to rapid testing of human drug responsiveness in a dish. The iPSC lines will also be expanded and banked by NYSCF and made available to the global scientific community to be used for research and the development of therapies.

Patrick Livney, CEO of the CMTA notes: "The Foundation has assembled the scientific and clinical key opinion leaders in CMT disorders, and the research tools necessary to validate therapeutic opportunities for their clinical potential. We have set out to engage drug makers to work together with the CMTA to advance new therapeutic approaches to our patients, and our STAR network that combines this world class research expertise with an operational capability has been highly enabling to the formation of collaborative alliances for this purpose. Currently, there are no therapies for the different CMT disorders to halt either the onset or progression of the disease. This NYSCF collaboration represents an exciting opportunity for the CMTA to place research on therapies for Charcot-Marie-Tooth disorders in a personalized, patient context at a very early stage.

"We are very exctied to partner with the Charcot-Marie-Tooth Association to develop resources that will enable the pursuit of new treatments and eventually cures for neruropathy disorders," said Susan L. Solomon, Co-Founder and CEO of NYSCF. "Partnering with CMTA provides us with the necessary community of scientists, patients, disease experts, as well as resources that allows us to move research forward. We believe that this type of interdisciplinary collaboration between various stakeholders is essential to to move research forward in the pursuit of cures."

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About Charcot-Marie-Tooth Association

The Charcot-Marie-Tooth Association (CMTA) is a registered 501c3 dedicated to serving an international patient community that suffers from rare and disabling neuropathies of genetic origin. The Foundation directly engages its STAR scientific and clinical research network in the identification, validation and clinical development of therapies for the different Charcot-Marie-Tooth disorders.

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NYSCF and the CMTA enter collaboration to advance neuropathies research

Microsoft billionaire takes on cell biology

By adminDecember 9, 2014Stem Cell Medical Center

Allen Institute

Paul Allens latest philanthropic endeavour will be modelled on his successful brain institute.

Billionaire businessman and philanthropist Paul Allen plans to pump US$100million into investigating the most basic unit of life the cell.

The Allen Institute for Cell Science, which was launched on 8 December, will be modelled on the Microsoft co-founders Allen Institute for Brain Science in Seattle, Washington, which since 2003 has spent hundreds of millions of dollars creating a series of brain atlases that have become go-to portals for neuroscientists interested in where particular genes are active or how distant neurons communicate.

As its first project, the latest Allen institute will develop an analogous cell observatory that will display how a cells working parts, such as ribosomes, microtubules and mitochondria, interact and operate over time, says executive director Rick Horwitz. He has shuttered his cell-biology laboratory at the University of Virginia in Charlottesville to lead the institute in Seattle, Washington. The 70 or so scientific staff who will join the institute will work together on the overall goals of the observatory to build a global view of the myriad activities inside cells rather than on their own interests. Its going to be much more like the Manhattan Project, Horwitz says.

Allen Institute

Rick Horwitz shut down his lab at the University of Virginia to lead the Allen Institute for Cell Science.

Mapping every little detail of every kind of cell is a tall order, even with the backing of the worlds 27th richest person. Our problem is that this thing could blow up on us. It could be very, very big, Horwitz says. Were going to make judicious decisions to try to contain it.

Some of those choices have already been made, after meetings this year with leading cell biologists. The institute will study human induced pluripotent stem cells (cells coaxed into an embryonic stem-cell-like state) as they differentiate in the lab into two cell types: heart-muscle cells called cardiomyocytes; and the epithelial cells that line body cavities. These tissues were chosen as much for their relevance to disease cardiomyocytes malfunction in heart disease and most cancers arise in epithelial tissues as for the ease with which they can be reproducibly generated and grown in the lab.

The institutes plan is to engineer many different cell lines and determine how different cellular components respond to stimuli such as infection or exposure to a drug. These data will then guide the construction of computer models aimed at predicting how cells operate under various conditions, and all the information gained will be made available online. The institute will also distribute its cell lines so that other scientists can build on its work.

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Microsoft billionaire takes on cell biology

New single-cell analysis reveals complex variations in stem cells

By adminDecember 4, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Kat J. McAlpine katherine.mcalpine@wyss.harvard.edu 617-432-8266 Wyss Institute for Biologically Inspired Engineering at Harvard @wyssinstitute

(BOSTON) -- Stem cells offer great potential in biomedical engineering due to their pluripotency, which is the ability to multiply indefinitely and also to differentiate and develop into any kind of the hundreds of different cells and bodily tissues. But the precise complexity of how stem cell development is regulated throughout states of cellular change has been difficult to pinpoint until now.

By using powerful new single-cell genetic profiling techniques, scientists at the Wyss Institute for Biologically Inspired Engineering and Boston Children's Hospital have uncovered far more variation in pluripotent stem cells than was previously appreciated. The findings, reported today in Nature, bring researchers closer to a day when many different kinds of stem cells could be leveraged for disease therapy and regenerative treatments.

"Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering," said the study's co-senior author James Collins, Ph.D., who is a Wyss Institute Core Faculty member, the Henri Termeer Professor of Medical Engineering & Science at MIT, and a Professor of Biological Engineering at MIT. "Now, we have discovered that what was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells."

The research team has learned that there are many small fluctuations in the state of a stem cell's pluripotency that can influence which developmental path it will follow.

It's a very fundamental study but it highlights the wide range of states of pluripotency," said George Daley, study co-senior author, Director of Stem Cell Transplantation at Boston Children's Hospital and a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. "We've captured a detailed molecular profile of the different states of stem cells."

Taking this into account, researchers are now better equipped to manipulate and precisely control which cell and tissue types will develop from an individual pluripotent stem cell or stem cell colony.

"The study was made possible through the use of novel technologies for studying individual cells, which were developed in part by collaborating groups at the Broad Institute, giving our team an unprecedented view of stem cell heterogeneity at the individual cell level," said Patrick Cahan, co-lead author on the study and Postdoctoral Fellow at Boston Children's Hospital and Harvard Medical School.

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New single-cell analysis reveals complex variations in stem cells

Researchers recreate stem cells from deceased patients to study present-day illnesses

By adminDecember 3, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-Dec-2014

Contact: Cara Martinez cara.martinez@cshs.org 310-423-7798 Cedars-Sinai Medical Center @cedarssinai

LOS ANGELES (Dec. 1, 2014) - Research scientists have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using DNA from stored blood samples to study the potential causes of debilitating illnesses such as inflammatory bowel disease.

The lab research, published in the journal STEM CELLS Translational Medicine, could yield new therapies for people who suffer from aggressive motor-neuron and gut-related conditions that proved fatal to the deceased patients who long-ago volunteered their blood samples.

"The potential implications of this research are vast," said Dhruv Sareen, PhD, the study's lead author, and assistant professor and director of the David and Janet Polak Foundation Stem Cell Core Laboratory in the Board of Governors Regenerative Medicine Institute.

By using a deceased patient's stored blood samples, Sareen and his colleagues found that they can develop stem cells known as iPSCs in a petri dish - essentially reanimating diseased cells from patients long after they have died.

This approach allows researchers to connect the dots between a deceased patient's symptoms, genetic information contained in DNA and the behavior of stem cells in the lab. This, in turn, enables investigators to study the biological mechanisms behind diseases and potentially design new therapies.

The technique also allows physicians to replace invasive biopsy procedures typically required of living patients to create iPSC cells.

"These novel developments allow us to create new lines of stem cells from literally millions of patient samples stored in large repositories," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute. "Some of these deceased patients were diagnosed with rare and important diseases."

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Researchers recreate stem cells from deceased patients to study present-day illnesses

World Stem Cell Summit kicks off in SA with Public Education Day

By adminDecember 3, 2014Stem Cell Medical Center

NEWS

1200+ scientists, patient advocates from 40 countries in town for summit

Posted YESTERDAY, 6:04 PM Updated YESTERDAY, 6:33 PM

SAN ANTONIO - More than a thousand scientists, industry leaders and patient advocates from 40 countries are headed to San Antonio for the World Stem Cell Summit.

Organizers are calling it the center of the universe when it comes to stem cells and regenerative medicine.

On Tuesday the summit kicked off with Public Education Day, where some of the smartest scientists in the field broke the topic down into bite-sized pieces.

"To be able to replenish our cells that die within a tissue on a daily basis, in order for us to be able to heal wounds, we have to have stem cells," said Elaine Fuchs, an investigator for the Howard Hughes Medical Institute.

She started her research in the field in the 1970s with work on skin stem cells, and said she was fascinated with creating skin in a petri dish that could then be used for burn therapy.

Fuchs spoke at Public Education Day about the most basic biology of stem cells and said that knowledge is leading to a new world in medicine.

"The biology of stem cells is gong to be and is being extremely valuable in terms of developing new therapies and coming up with new drugs to treat various different devastating diseases," Fuchs said.

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World Stem Cell Summit kicks off in SA with Public Education Day

A Swedish Scientist is Among the Recipients of the Hamdan Medical Award

By adminDecember 1, 2014Stem Cell Medical Center

DUBAI, December 1, 2014 /PRNewswire/ --

The Karolinska Institutet Professor Olle Ringdn, who is also the medical director at the Center for Allogeneic Stem Cell Transplantation at the Huddinge University Hospital in Stockholm, is a co-winner of the Hamdan Award for Medical Research Excellence, in the topic of Cell Therapy, sharing the prestigious Award with the American Professor Carl June.

(Photo: http://photos.prnewswire.com/prnh/20141201/719718 )

At a grand ceremony, H.H. Sheikh Hamdan Bin Rashid Al Maktoum, Deputy Ruler of Dubai, UAE Minister of Finance and the Patron of the Award will honor the Swedish Professor Ringdn alongside with 18 other winners of various categories of this Award at its 8th term (2013-2014).

Prof. Ringden devoted his life to treating patients with various life-threatening disorders. By endless hard work during four decades, he has substantial discoveries in a variety of research fields that led to decreased transplantation-related mortality and improved survival.

He established a stem cell research laboratory, where he, amongst other achievements, pioneered allogenic hematopoetic stem cell transplantation research in Sweden.

He conducted various comprehensive studies of the immune system, thus uncovering the compartmentalization of this system. Subsequent to his work, spleen cells are routinely used for immunological testing of deceased organ donors for transplantation.

Prof. Ringdn developed several immunosuppressive therapies to facilitate peripheral blood stem cell transfer from unrelated donors. He highlighted the potential value of mesenchymal stem cells in various transplantation regimens, and this is one of his numerous achievements in the field of stem cell transplantation.

He established bone marrow and allogenetic hematopoietic stem cell transplantation (AHSCT) in Sweden, and designated a research laboratory for this purpose. This laboratory was the nucleus for what became the Centre for Allogeneic Stem Cell Transplantation (CAST) in 1999, which is unique for this specialty in Northern Europe.

Prof Olle Ringdn changed the way immunomodulatory therapy is applied; by using cells from the patient, or from appropriate donors, to re-focus immune responses, heal inflammation, restore and rebuild tissues. This concept is now well embraced and practiced worldwide; helping to save the lives of many patients.

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A Swedish Scientist is Among the Recipients of the Hamdan Medical Award

Researchers Recreate Pain-Sensing Neurons

By adminDecember 1, 2014Stem Cell Medical Center

Researchers at the Harvard Stem Cell Institute and the Stem Cell and Regenerative Biology Department have successfully developed pain-sensing neurons from mouse and human skin cells, according to a report published in Nature Neuroscience in late November.

The study specifically aimed to simulate primary afferent nociceptors, very specialized pain-sensing neurons.

According to head researcher Clifford J. Woolf, a professor of Neurology and Neurobiology at theMedical School, the findings may lead to development of more effective pain medications, better methods to evaluate who is at risk for developing chronic pain, and ways to combat pain complications resulting from cancer chemotherapy.

What weve been able to do with stem cell technology for the first time is recreate some of the key elements of the nervous system by taking one cell and turning it into a particular other cell, Woolf said. This enables us for the first time to really dissect how human neurons function in the nervous system.

For Woolf, the study is a culmination of many years of research, previously done only in mouse cells.

The fact that we can even create these cells with a human gives us the opportunity to study the mechanisms of the way human nervous systems work that havent been possible before, Woolf said.

Tony L. Yaksh, co-director of the Pain and Symptom Management Core of the University of California at San Diegos Regional Cancer Center, emphasized the studys role in raising new questions for further research.

I think this is highly innovative and an extremely well-done paper, Yaksh said. Id say this represents a very concerted, well-organized group effort to define this very critical issue. It leaves you with more questions than before you read the paper, but it starts the ball rolling in a very exciting way.

Yaksh also highlighted the importance of the study in streamlining gene-specific treatment.

The significance is [that] this allows us to define a mechanism that may be relevant to pain transmission in humans without having to euthanize a human being, Yaksh said.

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Researchers Recreate Pain-Sensing Neurons