Category Archives: Wisconsin Stem Cells

Dec 15, 2014 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

PUBLIC RELEASE DATE:

6-Dec-2014

Contact: Amanda Szabo aszabo@hematology.org 415-978-3620 American Society of Hematology @ASH_hematology

(SAN FRANCISCO, December 6, 2014) - New treatment combinations and targeted therapies for lymphoma and multiple myeloma are improving outcomes for vulnerable patient populations with hard-to-treat disease, according to studies presented today at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

Despite advances in lymphoma treatments, improving the prognosis for patients with relapsed and treatment-resistant disease remains a challenge. The early success of several precision therapies associated with fewer side effects than conventional approaches offers new hope for conquering aggressive disease. For lymphoma patients who relapse or do not respond to initial therapy, stem cell transplantation also presents a potentially curative option; however, this procedure is not always successful. Two studies presented today detail methods to improve outcomes in patients with relapsed or hard-to-treat lymphoma, including adding a targeted antibody to standard treatment to prevent relapse after transplant, and an approach to making stem cell transplantation the standard of care for patients with HIV-associated lymphoma.

In three other studies, researchers will describe new advances in the treatment of myeloma. These reports are examples of new precision treatments, including a proteasome inhibitor and two anti-CD28 antibodies that demonstrate encouraging results when combined with standard care for patients with relapsed and treatment-resistant disease.

"While eradicating aggressive lymphoma and multiple myeloma remains a major hurdle, the emergence of several promising strategies makes this an exciting time for physician-scientists in this field," said Brad Kahl, MD, moderator of the press briefing and Associate Professor of Medicine at the University of Wisconsin School of Medicine and Public Health in Madison. "By combining therapies and studying outcomes in vulnerable subsets of patients, we are learning more about how we can best help those who have not responded to any other treatment."

This press briefing will take place at 8 a.m. PST on Saturday, December 6, in rooms 236-238 of Moscone South, East Mezzanine.

Brentuximab Vedotin Prolongs Post-Transplant Survival in Hard-to-Treat Lymphoma Patients in Phase III Study

The AETHERA Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma Study [673]

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Advances in lymphoma and multiple myeloma treatment seek to improve outcomes for patients

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Newswise New York, New York Research to Prevent Blindness (RPB), the leading eye research foundation, is partnering with the International Retinal Research Foundation (IRRF) to advance knowledge about age-related macular degeneration (AMD) through novel stem cell research. RPB/IRRF & RPB Sybil B. Harrington Catalyst Awards for Stem Cell Research Approaches for Age-Related Macular Degeneration (the Catalyst Awards) have been given to three leading researchers. Each will receive $250,000 over four years. Research related to both dry and wet forms of AMD is supported by these awards.

Said RPB President Brian F. Hofland, PhD: The concept for these partnership grants evolved out of a significant gift that we received from an anonymous donor who wanted us to focus on stem cell research and AMD. It came with the condition that we would find matching funding. We found a valuable partner in the International Retina Research Foundation very quickly for two of the awards, and one we matched with bequest money that we received from the Sybil Harrington Estate a generous family that is committed to health-related research on several fronts. We are especially encouraged that this all came together at a key time in the field of stem cell research, and we are hopeful that these three awards together will indeed be a catalyst for breakthroughs in this area.

There also will be a collaborative learning component that will have the three researchers work together and share information on areas of mutual interest and overlap, according to Hofland.

We are incredibly excited about the potential impact on AMD stem cell therapies that could result from this partnership, adds Sandra Blackwood, Executive Director, IRRF. RPB and IRRF both seek to accelerate vision science discoveries that could lead to life-changing treatments for patients who have lost sight. By pooling our resources we can better meet the needs of the scientists who are doing the actual heavy lifting.

Stem cell-based, sight-restoring therapies may become available for patients with eye diseases in the next few years, says Jeffrey Goldberg, MD, PhD, University of California, San Diego, and a member of RPBs Scientific Advisory Panel. But there are still hurdles to overcome. The Catalyst Award recipients are working on critical aspects of those issues and could significantly accelerate the efficacy of those treatments.

These Catalyst Awards provide seed funding for high-risk/high-gain innovative, cutting-edge vision science research conducted by:

David M. Gamm, MD, PhD, RPB/IRRF Catalyst Awardee, University of Wisconsin School of Medicine, whose goal is to optimize transplanted retinal pigmented epithelium cell survival based on an innovative hypothesis. Gamm is a leader in the RPE stem cell transplantation field. Cell survival is critical to the success of RPE transplantation as a therapy for retinal degenerative diseases. Akiko Maeda, MD, PhD, RPB Sybil B. Harrington Awardee, Case Western Reserve University, who proposes to test the validity of induced pluripotent stem cell (iPSC)-derived retinal 3D-optic cups as platforms for individualized drug screening for AMD patients. The combination of stem cell and pharmacologic approaches greatly increases the potential for translation of the concepts under investigation into treatments for patients. Budd A. Tucker, PhD, RPB/IRRF Catalyst Awardee, University of Iowa Carver College of Medicine, whose main objective is to produce outer retinal cell grafts (grown from fibroblasts taken from a patients own skin) on biodegradable scaffolds and deliver the cell scaffolds into an eye. This work could solve two problems facing cell transplantation methods today: immune response, and the enormous loss of cells that occurs following bulk injection of stem cells into the eye.

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Research to Prevent Blindness, Inc. and the International Retinal Research Foundation Announce Catalyst Awards for AMD ...

Director of Regenerative Biology, Morgridge Institute for Research / Professor of Cell and Regenerative Biology (UW) / Professor, Molecular, Cellular, and Developmental Biology - University of California, Santa Barbara

In the early 1990s, my lab derived ES cells from an Old World monkey (the rhesus macaque) and a New World monkey (the common marmoset), work that led to derivation of human ES cells in 1998. Much of my labs research after that derivation was dedicated to establishing human ES cells as an accepted, practical model system. To that end, we developed defined culture conditions, methods for genetic manipulation, and approaches for the in vitro differentiation of human ES cells to key lineages of clinical importance including hematopoietic, neural, cardiac, and placental tissues. More recently, in 2007, my laboratory described the isolation of human induced pluripotent (iPS cells) cells with the basic properties of human ES cells but derived from somatic cells.

My research now focuses on understanding how a cell can maintain or change identity, how a cell chooses between self-renewal and the initial decision to differentiate, and how a differentiated cell with limited developmental potential can be reprogrammed to a pluripotent cell.

My current research interests include:

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James A. Thomson - Wisconsin Stem Cell Research Program

Developmental and Regenerative Biology graduate program

The Department of Cell and Regenerative Biology is pleased to announce the establishment of a new graduate program (Fall 2012) to provide training in the areas of Developmental and Regenerative Biology (DRB). Students admitted via other Ph.D. programs (UW Graduate School Admissions) will fulfill the requirements of the admitting program in parallel to the DRB curriculum in order to receive a Ph.D. from the admitting program in addition to a certificate in Developmental and Regenerative Biology. Core DRB courses include: 1) Fundamentals of Stem Cell Biology and 2) Stem Cells and Regenerative Biosciences Roundtable. Electives include: 1) Mammalian Embryology and 2) Molecular and Cellular Organogenesis. For additional information contact the DRB program chair, Grace Boekhoff-Falk (boekhofffalk@wisc.edu).

Figure (right): Neural stem cells (arrowheads) and newly born neurons (arrow) in the developing mushroom body of the Drosophila brain (J. Plavicki and G. Boekhoff-Falk) (Click to enlarge)

Molecular and Cellular Pharmacology Graduate Program

The objective of the Graduate Program in Molecular and Cellular Pharmacology (MCP) is to equip students with expertise in cell biology and cell signaling cascades, with a focus on identifying targets and developing techniques for therapeutic interventions in human disease. Thus, students will develop the skills required to conduct state-of-the-art cell biology, biomolecular, biomedical, and pharmacological basic research: the fundamentals of Molecular and Cellular Pharmacology. Students who obtain a Ph.D. through the MCP Program (there is no formal MCP Masters degree) will be able to solve a variety of problems in basic biomedical sciences involving the design of research strategies for the discovery of novel drugs or gene therapy approaches to regulate signal transduction cascades and cellular behaviors. Patrica J. Keely, Ph.D., Associate Professor of Cell and Regenerative Biology, is the director of the this interdepartmental, interdisciplinary program. For further information regarding the MCP program, please visit the link below: Molecular and Cellular Pharmacology Graduate Program

Or contact: Lynn L. Squire Senior Student Services Coordinator Molecular and Cellular Pharmacology Graduate Program Room: 3770 Medical Sciences Center 1300 University Ave Madison, WI 53706 lsquire@wisc.edu (608) 262-9826

University of Wisconsin Stem Cell & Regenerative Medicine Center

Beginning in 1995 with the first successful culturing of embryonic stem cells from non-human primates, and later with the isolation of the world's first human embryonic stem cells, the University of Wisconsin-Madison has been a leader in the companion fields of stem cell research and regenerative medicine. The UW-Madison Stem Cell and Regenerative Medicine Center (SCRMC) is an umbrella organization operating under the School of Medicine and Public Health and the Graduate School. A number of faculty members of the Department of Cell and Regenerative Biology are also members of the SCRMC, which provides a central point of contact, information and facilitation for all stem cell research activities on campus. The center's mission is to advance the science of stem cell biology and foster breakthroughs in regenerative medicine through faculty interactions, research support and education. For further information regarding the MCP program, please visit the link below: http://stemcells.wisc.edu/

University of Wisconsin Cardiovascular Research Center

Cardiovascular research is an historically important aspect of research activities at the University of Wisconsin School of Medicine and Public Health.

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Programs - Cell and Regenerative Biology, University of ...

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Newswise One remarkable quality of pluripotent stem cells is they are immortal in the lab, able to divide and grow indefinitely under the right conditions. It turns out this ability also may exist further down the development path, with the workhorse progenitor cells responsible for creating specific tissues.

A team from the Morgridge Institute for Research regenerative biology group, led by University of Wisconsin-Madison professor and stem cell pioneer James Thomson, discovered a way to impose an immortal-like state on mouse progenitor cells responsible for producing blood and vascular tissue. By regulating a small number of genes, the cells became trapped in a self-renewing state and capable of producing functional endothelial, blood and smooth muscle cells.

The finding, to be published in the December 9, 2014 issue of Stem Cell Reports, points to a potential new approach to developing cells in the lab environment for use in drug screening, therapies and as a basic research tool.

The biggest takeaway for me is the ability to arrest development of these cells, says David Vereide, a Morgridge fellow in regenerative biology and lead author on the paper. Normally, these cells are ephemeral and get used up while differentiating into specific cell types, but we found a way to interrupt that.

During development, blood and vascular cells are thought to originate from a progenitor cell known as a hemangioblast. This research project identified and imposed six transcription factors on the cells that allowed hemangioblasts to keep proliferating over multiple generations. Transcription factors are proteins that regulate which genes get turned on or off in a genome.

In this case, the transcription factors act to keep the lights on in these cellular factories that kept them dividing and expanding, he says.

One exciting element of this research, Vereide says, is it could greatly improve the efficiency of creating cell types that have research and therapeutic value.

Progenitor cells, the sons and daughters of stem cells that give rise to specific tissue, are usually the end steps in producing the key building-block cells for the body brain, vasculature, bone, etc.

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Morgridge Scientists Find Way to 'Keep the Lights on' for Cell Self-Renewal

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BioEden the leading tooth stem cell bank records a 45% increase in global sales in October

(PRWEB UK) 9 November 2014

Every day stem cell treatments are in the news, often bringing the last hope for many patients with serious conditions that have defied traditional medicine.

BioEden's Group CEO Tony Veverka says, 'the increase in popularity in banking a persons own cells is as a result of two main things; 1. The likelihood of needing stem cell therapy is high, and 2. You need a stem cell match - your own cells are the perfect match'.

BioEden's tooth stem cell banking service is the only way you can access your own cells without the need for medical intervention. More and more parents are choosing to bank their children's stem cells as the baby tooth is shed naturally. However, stem cells can be banked from a healthy adult molar, that perhaps is being removed for orthodontic reasons.

Obtaining stem cells from other sources such as bone marrow is not only invasive but costly. Taking the decision to bank ones own cells is a sensible consideration, and costs from just 295.

For the original version on PRWeb visit: http://www.prweb.com/releases/2014/11/prweb12312890.htm

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BioEden the specialist tooth stem cell bank announce ...

PUBLIC RELEASE DATE:

29-Oct-2014

Contact: Caroline Marin crmarin@umn.edu 612-624-5680 University of Minnesota Academic Health Center @UMN_Health

MINNEAPOLIS-ST. PAUL (October 29, 2014) A new standard of care for children facing acute myeloid leukemia (AML) may be clear, following a multi-year study published in the latest edition of the New England Journal of Medicine.

The research, led by John Wagner, Jr., M.D., director of the Pediatric Blood and Marrow Transplantation program at the University of Minnesota and a researcher in the Masonic Cancer Center, University of Minnesota, compared outcomes in children with acute leukemia and myelodysplastic syndrome who received transplants of either one or two units of partially matched cord blood. The study was conducted at multiple sites nationwide, between December 2006 and February 2012. Coordinating the study was the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) in collaboration with the Pediatric Blood and Marrow Transplant Consortium and the Children's Oncology Group.

While the study found similar survival rates in both arms of the study, survival was overall better than in prior reports. This could create a new standard of care for pediatric patients for whom there is often an adequate single unit and adults for whom there is the need for a double unit should a single unit with an adequate number of blood forming stem cells may not exist.

Umbilical cord blood, a rich source of blood-forming stem cells, has previously been shown to benefit many patients with leukemia and myelodysplasia and other diseases, including bone marrow failure syndromes, hemoglobinopathies, inherited immune deficiencies and certain metabolic diseases. Cord blood offers several advantages for leukemia patients there is no need for strict human leukocyte antigen (HLA) matching and or prolonged search for a donor.

"Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood forming stem cells in two cord blood units might improve survival," explained Wagner. "What we found, however, was that both treatment arms performed very well with similar rates of white blood cell recovery and survival."

Children with blood cancer have previously been shown to benefit from umbilical cord blood, despite HLA mismatch, making it an important alternative for patients who cannot find a matched unrelated donor. However, the limited number of cells in a single cord blood unit obtained from a placenta after the birth of a child, has often curbed its potential benefits. The double UCB approach was pioneered at the University of Minnesota as a strategy to overcome this limitation.

Despite the similarities in survival rates, some differences were noted. Children transplanted with a single cord unit had faster recovery rates for platelets, the cell components important in clotting, and lower risks of GVHD, a condition where the transplanted donor blood immune cells recognize the patient's body as foreign causing a number of complications.

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Survival rates in pediatric umbilical cord transplants may indicate a new standard of care

Maria Estevez, a UW-Madison senior majoring in biomedical engineering, has been a research assistant in one of the Wisconsin Institutes for Discoverys BIONATES labs for the last three years, working to advance stem cell use and regenerative medicine through innovations in engineering.

Estevez works on re-engineering human embryonic stem cells to function as brain cells. These new cells are then used to model and study diseases that affect the human brain.

More notable than Estevezs unique experience in such a rising field, however, is her position as a woman in research.

Having been a teachers assistant in an introductory engineering lecture, Estevez has seen some of the patterns in class demographics first-hand.

A lot of girls start coming into the intro to engineering classes, but you go through the years and, class by class, there are less of them, Estevez said.

These concerns aside, Estevez acknowledged that efforts by the College of Engineering and the WID to attract more girls to science, technology, engineering and mathematics fields have been effective.

As an example, she pointed to private tutoring offered by the College of Engineering specifically for female and minority students enrolled in STEM classes, which she considers one of the most useful opportunities available to historically underrepresented students in these fields.

She added that all students have the same faculties, but lack of support, encouragement and the presence of psychological barriers can often affect different people in different ways. Therefore, she said this kind of tutoring has the potential to be incredibly helpful in closing the achievement gap and increasing retention rates.

Perhaps the biggest hurdle facing women, Estevez contended, is balancing priorities. Sometime in their lives women must make decisions about family and choices about their roles at home, she said.

Perhaps considering her own varied interests, such as a mission trip she hopes to take in the future, Estevez said it is important for women to find meaningful work they are passionate about.

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UW-Madison senior Maria Estevez discusses women pursuing STEM fields

MADISON Winning the State Cow of the Year award at the 2014 World Dairy Expo on Oct. 3 was only the second biggest thing that happened while the Peterson family of Cashton was in Madison that week.

The most important came a few days later, on the west side of the University of Wisconsin-Madison campus, when stem cells from Kurt Petersons bone marrow began flowing into the blood stream of his brother, giving Scot Peterson, 45, a new immune system and a good shot of beating adult acute lymphoblastic leukemia (ALL).

Hes a man of few words, says Scot, of his younger brother, Kurt, 40. But you know he really loves you to do something like this.

Its been a good news/bad news kind of a year for the Peterson brothers, who co-own the Coulee Crest farm in the rolling hills of Monroe County, and the states queen of cows, Coulee Crest Nick Lorilyn. Guernseys are the caramel brown and white cows known for the richness of their milk. And Lorilynn won the crown because she, her mother, and one of her daughters have each produced 40,000 pounds of milk in a year.

The last weekend in June, the National Guernsey Association held its national convention in La Crosse. The Petersons hosted a tour of their farm and a dinner event for 475 convention goers at their farm.

Scot Peterson, a burly guy who competed in Sweden for the world tug-of-war championship when he was younger, felt pains in his legs, odd bruises, and general exhaustion.

I thought I was tired from all the work of getting the farm ready, Scot Peterson says. He got through the convention and the national sale on June 30. That was another high point for the farm, with one of Lorilyns daughters topping the sale at $19,000.

By the next day, there was bad news.

By the middle of the day on July 1, I was in the hospital, finding out my diagnosis of leukemia, he recalls.

His oncologist, Dr. Wayne Bottner of Gundersen Health System in La Crosse, told Scot that he had a type of leukemia, ALL, in which the bone marrow makes too many lymphocytes, a type of white blood cell. ALL is more common and easier to treat in children. Adults fare better if they can find a match that allows them to have a stem cell transplant from a donors bone marrow. So Bottner referred Peterson to the UW Carbone Comprehensive Cancer Center in Madison.

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Cashton man goes from winning state award to battling cancer