Category Archives: Minnesota Stem Cells

asakura@umn.edu

Dr. Atsushi Asakura is an Associate Professor of Neurology and a faculty member of the Stem Cell Institute in the University of Minnesota Medical School. He also belongs to Paul & Sheila Wellstone Muscular Dystrophy Center in the Medical School.

Dr. Asakura received his Ph.D. at the Institute of Medical Science at the University of Tokyo Graduate School and the National Institute of Neuroscience in Tokyo with Dr. Yo-ichi Nabeshima where he learned the molecular biology of skeletal muscle differentiation.

He trained at the post-doctoral level at the Fred Hutchinson Cancer Research Center in Seattle with Dr. Stephen J. Tapscott. His post-doctoral studies involved the transcription factors for skeletal muscle development during early embryogenesis.

He trained at the senior post-doctoral level at McMaster University in Hamilton and the Ottawa Health Research Institute in Ottawa with Dr. Michael A. Rudnicki where he started projects on skeletal muscle stem cells that contribute to muscle regeneration.

My laboratorys goals include attempting to understand the molecular mechanisms controlling muscle satellite cell (muscle stem cell) self-renewal and differentiation, and to develop novel therapeutic methods for Duchenne Muscular Dystrophy (DMD). This also involves the stem cell niche associated with vasculature in normal and regenerating skeletal muscle. And, we have recently begun exploration of cell based therapy with induced Pluripotent Stem Cells (iPSCs) toward muscular dystrophy model animals and heart infarction models.

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Atsushi Asakura, Ph.D. - MED - Stem Cell Institute ...

Released: 9-Mar-2015 10:05 AM EDT Embargo expired: 10-Mar-2015 5:00 PM EDT Source Newsroom: Tufts University Contact Information

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Newswise MEDFORD/SOMERVILLE, Mass. (March 11, 2015) -- Research reported today by Tufts University biologists shows for the first time that bioelectrical signals among cells control and instruct embryonic brain development and manipulating these signals can repair genetic defects and induce development of healthy brain tissue in locations where it would not ordinarily grow.

The research reveals that bioelectric signaling regulates the activity of two cell reprogramming factors (proteins that can turn adult cells into stem cells), which for the first time were analyzed in Xenopus laevis embryos, which share many evolutionary traits with humans. Results appear in the March 11, 2015, edition of the Journal of Neuroscience.

"Weve found that cells communicate, even across long distances in the embryo, using bioelectrical signals, and they use this information to know where to form a brain and how big that brain should be," says the papers corresponding author Michael Levin, Ph.D., who holds the Vannevar Bush Chair in biology and directs the Center for Regenerative and Developmental Biology in the School of Arts and Sciences at Tufts. "The signals are not just necessary for normal development; they are instructive."

Levin uses an analogy to a computer. "Bioelectrical signals are not simply the switch that turns the computer on or off, passively allowing it to perform its functions. They actually carry important information, functioning like the software that enables the computer to carry out complex activities."

These bioelectric signals are implemented by changes in the voltage difference across cell membranes called the cellular resting potential -- and the patterns of differential voltages across anatomical regions.

Bioelectric signaling involves different cell types, including mature somatic cells and stem cells. Prior work in the Levin lab revealed roles for bioelectric gradients in eye, limb and visceral organ patterning, and the new paper found that natural embryonic voltage gradients instruct the formation of the brain.

Overriding Genetic Defects "This latest research also demonstrated molecular techniques for 'hijacking' this bioelectric communication to force the body to make new brain tissue at other locations and to fix genetic defects that cause brain malformation," says Levin. "This means we may be able to induce growth of new brain tissue to address birth defects or brain injury, which is very exciting for regenerative medicine."

A case in point is the Notch signaling pathway, a protein signaling system that plays a role in neural cell growth and differentiation in mammals and most other multicellular organisms. Defects in Notch signaling disrupt brain development and are also associated with disorders such as T-cell acute lymphoblastic leukemia and multiple sclerosis. The research team found that using molecular techniques to force proper bioelectrical states in cells enabled them to override the defects induced by Notch malfunction, resulting in a much more normal brain despite a genetically-defective Notch protein.

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Bioelectricity Plays Key Role in Brain Development & Repair

Institute Director

tolar003@umn.edu

Education

Dr. Tolar is an Associate Professor of Pediatrics at the University of Minnesota in the Division of Blood and Marrow Transplantation, and an attending physician at the University of Minnesota Amplatz Childrens Hospital Fairview. Dr. Tolar is trained both in basic science and in medicine. He received his M.D. from Charles University in Prague, Czech Republic, and his Ph.D. in Molecular, Cellular, Developmental Biology and Genetics from the University of Minnesota. He completed a residency in Pediatrics and a fellowship in hematology/oncology and bone marrow transplantation at the University of Minnesota. He is board certified in Pediatric Hematology/Oncology. Dr. Tolar has been the Director of Stem Cell/Gene Therapies in the Division of Blood and Marrow Transplantation since 2011.

Dr. Tolar's research focuses on stem cell therapy for patients with lethal diseasescancer, inborn errors of metabolism, and devastating genetic disorders.

Research Interests

In the laboratory, he is currently working on inducing pluripotency in a variety of cell types and creating human disease models in a dish at the cellular level. He is also investigating gene editing using sequence-specific nucleases. Dr. Tolars primary motivation is improving patient care and the clinical translation of tissue stem cell and regenerative biology. He has several clinical trials that focus on the efficacy and safety of new treatments for diseases like epidermolysis bullosa and dyskeratosis congenita. He also leads the International Fanconi Anemia Gene Therapy Working Group.

Selected Recent Publications

Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. N Engl J Med. 2010;363(7):629-39.

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Jakub Tolar, M.D., Ph.D. - MED - Stem Cell Institute ...

Stem cells are truly remarkable. They bridge the gulf between the fertilized egg that is our origin and the architecture that we become. They supply the cells that construct our adult bodies and, as we age, replenish worn out, damaged and diseased tissues. They renew themselves, resisting the powerful pull towards differentiation that overcomes more prosaic cells. And depending on the source, they have the potential to form one, many or all cell types of an organism.

Stem cell research has a history of more than 20 years, and has made some outstanding contributions to our understanding of haematopoiesis and mouse embryology. But the field has been transformed in the past few years by successes achieved in culturing human embryonic stem cells, the building blocks for every tissue we comprise, and in manipulating their differentiation in vitro. This web focus encompasses a one-stop shop for a selection of excellent articles and features on stem cells handpicked from the pages of Nature, including the specially commissioned Stem Cell Insight.

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease JONG-HOON KIM , JONATHAN M. AUERBACH , JOS A. RODRGUEZ-GMEZ , IVN VELASCO , DENISE GAVIN , NADYA LUMELSKY , SANG-HUN LEE , JOHN NGUYEN , ROSARIO SNCHEZ-PERNAUTE , KRYS BANKIEWICZ & RON MCKAY Nature AOP published online 20 June 2002; doi:10.1038/nature00900 | First Paragraph | Full Text (HTML / PDF) |

Pluripotency of mesenchymal stem cells derived from adult marrow YUEHUA JIANG , BALKRISHNA N. JAHAGIRDAR , R. LEE REINHARDT , ROBERT E. SCHWARTZ , C. DIRK KEENE , XILMA R. ORTIZ-GONZALEZ , MORAYMA REYES , TODD LENVIK , TROY LUND , MARK BLACKSTAD , JINGBO DU , SARA ALDRICH , AARON LISBERG , WALTER C. LOW , DAVID A. LARGAESPADA & CATHERINE M. VERFAILLIE Nature AOP published online 20 June 2002; doi:10.1038/nature00870 | First Paragraph | Full Text (HTML / PDF) |

Biomedicine: Stem-cell competition STUART H. ORKIN & SEAN J. MORRISON The debate continues over the relative merits of using embryonic and adult stem cells for research and perhaps, one day, to treat patients. Two new papers look at the abilities of these remarkable cells. Nature 418, 2527 (4 July 2002) | Full Text | PDF |

Stem cell hopes double Embryo and adult stem cell findings may re-fuel cloning research debates | Link |

Stem cells hype and hope RON MCKAY Nature 406, 361364 (2000); doi:10.1038/35019186 | Full Text (HTML / PDF) |

Can they rebuild us? PETER ALDHOUS The idea of therapeutic cloning, which offers the potential of growing replacement tissues perfectly matched to their recipients, is falling from favour. But there are alternatives, as Peter Aldhous found out. Nature 410, 622625 (2001); doi:10.1038/35070659 | Full Text (HTML / PDF) |

Stem cells | Link |

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Stem Cell Web Focus - Nature Publishing Group : science ...

Updated DEC 19, 2014 6:19p ET

Call it a Christmas miracle. That's pretty much the way Gordie Howe's family is describing his extraordinary recovery -- thanks to an experimental stem-cell treatment -- from a series of strokes that appeared to threaten the 86-year-old hockey legend's life only a few weeks ago.

"This is truly a Christmas miracle," said Dr. Murray Howe, a Toledo physician and one of Gordie's four children. "I would not have believed it if I hadn't seen it with my own eyes. "

Howe, gravely ill at the time, underwent the treatment on Dec. 8 in San Diego.

"As a family, we are thrilled that Dad's quality of life has greatly improved, and his progress has exceeded our greatest expectations," the Howe family said Friday in a news release in which it thanked a legion of fans praying for its father's recovery. "Once again, we cannot emphasize how much you have fueled Mr. Hockey's recovery, and we thank everyone for their continued prayers and support."

The neural stem cells were injected into the spinal canal on Day 1 and mesenchymal stem cells by intravenous infusion on Day 2, according to the release.

"His response was truly miraculous," the family said. "At the end of Day 1, he was walking with minimal effort for the first time since his stroke. By Day 2, he was conversing comfortably with family and staff at the clinic. On the third day, he walked to his seat on the plane under his own power."

Just five days later, Howe was walking unaided and even taking part in daily household chores, according to the release.

When tested, his ability to name items has gone from less than 25 percent before the procedure to 85 percent today, the release said.

"His physical therapists have been astonished," the family said. "Although his short-term memory, strength, endurance and coordination have plenty of room for improvement, we are hopeful that he will continue to improve in the months to come."

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Family: Experimental stem-cell treatment does wonders for Gordie Howe

Doctors at the University of Minnesotas childrens hospital traded in their white coats for ones embroidered with a new name.

With its $25 million donation, the Minnesota Masonic Charities became the Universitys largest donor, and in honor of the gift, the campuss pediatric hospital was renamed Tuesday as the University of Minnesota Masonic Childrens Hospital.

The donation will primarily go toward finding cures and treatments for childhood diseases, said Eric Neetenbeek, Minnesota Masonic Charities president and CEO.

The gift will specifically enhance patient and family experiences, as well as advance pediatric research on neurobehavioral development, rare and infectious disease, and stem cell therapy.

Dr. Joseph Neglia, the hospitals physician-in-chief, said he hopes the gift will create stronger relationships with pediatrics researchers across the University.

Really, to build new bridges is one big part of what Id like us to do, Neglia said. These gifts are vitally important for the hospital.

With the donation, Neglia said he also hopes to expand the hospitals existing research, like its work on correcting genetic defects in human cells and its pediatric medicine international programs in Kenya and Uganda.

Neetenbeek said the Masons donations, which total $125 million over the last 60 years, have been essential at a time when new health care research struggles to receive competitive funding from larger organizations like the National Institutes of Health.

There arent too many venture capitalists willing to go with untried businesses [and] ideas, he said. The same is true when youre looking at research into health care problems.

In the near future, the Masons will meet physicians at the childrens hospital to discuss which promising research projects to allocate the money toward, Neetenbeek said.

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Childrens hospital gets $25M

Updates from the recent annual scientific conference organised by the Society for Anti-Ageing, Aesthetics and Regenerative Medicine Malaysia.

THE Society for Anti-Ageing, Aesthetics and Regenerative Medicine Malaysia (SAAARMM) had its annual scientific conference recently, and I would like to share some of the updates.

You will notice that the society has a long name. It started as just an anti-ageing society. Then aesthetics was added because the demand for aesthetic therapies actually exceeds that of anti-ageing therapies. While most people want to look young, not all of them are concerned about being young (ie healthy). Finally, regenerative medicine was added.

Anti-ageing medicine implies the slowing down or reversal of ageing in an otherwise healthy person, while regenerative medicine implies the restoration of health and functions in the unhealthy or diseased person. Once health is restored, any further gain would be anti-ageing. These are strategies applied at different points of the health spectrum.

I try not to miss the annual convention because I always get to meet two of the pioneers and leading researchers/proponents in this field. Both are from the US.

Dr Bob Goldman is the chairman and co-founder of the American Academy of Anti-Aging Medicine (A4M), which is hugely responsible for popularising and promoting anti-ageing medicine throughout the world. He also holds the world record for hand-stand push-ups (doing push-ups with the body vertically up, head down).

Dr Nick Delgado is one of my mentors. He worked with the famous Pritikin Longevity Centre and also with top performance coach Anthony Robbins. Among other things, he taught me the goodness of whole-food juicing. He has his own range of supplements and anti-ageing strategy The Delgado Protocol. At the age of 54, he is the world champion for vertical lifts (repetitive lifting of 25-pound weights on alternate arms) and continues to defend his title. He is also pioneering the use of stem cells for rejuvenation, and uses himself as a guinea-pig, getting the injections every month. Already he has more hair than last year. He hopes to live to 150!

The three of us are of the same age (so is Dr Ronald Klatz, President and co-founder of A4M). So it will be interesting to see how we age over the years. All three of us rely on hormone optimisation/balancing and nutritional supplements. They are super-fit and super-strong individuals, while I only go to the gym whenever possible. I have to rely on my qigong to keep up with them. And soon I will have to start injecting stem cells into myself too.

Rejuvenation strategies

The basis of health and rejuvenation has always been a healthy lifestyle, a nutritious diet, and adequate exercise. And may I add, enough life-force, or qi. Every other strategy is additional to these basic requirements.

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Stem Cell Malaysia Blog

10 hours ago by Cheryl Chng

Temasek Life Sciences Laboratory, Hokkaido University and Ehime University are pleased to announce that their researchers have discovered that the reduction of gonadal stem cells will yield more male zebrafish. The article reporting this finding has been published online in Stem Cell Reports today.

These results indicate that a certain number of these specialized gonadal stem cells (primordial germ cells or PGCs) is required for ovary formation. Reduced PGC numbers result in more males, as some of the females are forced to change their sex permanently without affecting their fertility, indicating that PGC count plays a regulatory role during sexual differentiation in zebrafish. The findings suggest that a stem cell counting mechanism in the zebrafish gonad is important for determining sexual development, which provides new insight in vertebrate germline biology.

The sex ratio of cultured stocks is an important aspect of aquaculture, as there are distinct differences (e.g. size, colour, maturation, etc.) between the two sexes in several fish species. This discovery may provide potential tools for improved sex control of fishes in farms in the future.

Brief Summary of Research

There are more fish species on Earth than all other vertebrates combined. Fishes are very diverse not only in their external appearance, but also in the way their sexual development is controlled. Zebrafish are small-bodied ornamental fish that have become an important model for vertebrate biology over the past four decades. Every zebrafish individual starts to develop as an immature female, and future males must undergo a 'gonadal transformation' to produce functional testes. The molecular regulation of this process appears to be complex and poorly understood.

In an article that appears online in Stem Cell Reports (Cell Press), researchers from Temasek Life Sciences Laboratory (Singapore) in collaboration with Japanese scientists from Hokkaido University and Ehime University reveal that the number of PGCs plays a regulatory role during sexual differentiation in zebrafish. Using different methods and zebrafish lines, they demonstrate that a reduction in the number of PGCs results in more males presumably by forcing some of the females to change their sex permanently without affecting their fertility.

"These data show that a PGC counting mechanism in the gonad determines sexual development, giving rise to the hypothesis of PGC dosage-dependent sex differentiation. This provides a novel perspective to research on sexual development of fishes and a new insight in vertebrate germline biology" said Associate Professor Rie Goto at Ehime University.

"Better understanding of this 'gonadal switch' in zebrafish might eventually lead to improved tools for sex control in cultured fish species, especially in 'sex changing' food fishes, such as the groupers or Asian seabass, and improvements in their farm-based culture" commented Professor Lszl Orbn, Senior Principal Investigator at Temasek Life Sciences Laboratory.

Explore further: New method to grow zebrafish embryonic stem cells can regenerate whole fish

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Reduction of germ cells yields more zebrafish males

CHART-2 is Cardio3 BioSciences second Phase III trial for C-Cure, the first and only stem cell therapeutic using guided stem cells for the condition of congestive heart failure. C-Cure is currently in a Phase III clinical trial in Europe (CHART-1). The CHART-2 Phase III trial is a prospective, multi-centre, randomized, sham-controlled, patient- and evaluator-blinded study comparing treatment with C-Cure to a sham treatment. The trial is designed to recruit a minimum of 240 patients with chronic advanced symptomatic heart failure.

In a clinical trial, the Principal Investigator (PI) is responsible for the scientific and medical supervision of the trial. The PI reviews the protocol, oversees the implementation of the trial at all the investigational sites, and provides guidance as to the integrity and the interpretability of the data generated during the trial.

Dr Christian Homsy, CEO of Cardio3 BioSciences, said: Cardio3 BioSciences is very proud to count three such prominent physicians as the Co-Principal Investigators of its phase III clinical study for C-Cure authorized in the United States. The medical community is eagerly waiting for a solution for the treatment of heart failure patients, and CHART-2 is a promising avenue towards treating this disease. We selected three prominent cardiologists with established reputations and their acceptance to lead our clinical trial is further recognition of the potential of C-Cure as future treatment of heart failure.

*** END ***

To subscribe to Cardio3 BioSciences newsletter, visit http://www.c3bs.com. Follow us on Twitter @Cardio3Bio.

About CHART-2 CHART-2, the Company's second Phase III clinical trial, is intended to assess in the US, the efficacy of C-Cure as a treatment for heart failure of ischemic origin. CHART-2 is designed as a prospective, multi-centre, randomized, sham-controlled, patient- and evaluator-blinded study comparing treatment with C-Cure to a sham treatment. The trial is aimed to recruit a minimum of 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is the Six Minute Walk Test post-procedure, a commonly used index of cardiovascular performance.

About C-Cure Cardio3 BioSciences C-Cure therapy involves taking stem cells from a patients own bone marrow and through a proprietary process called Cardiopoiesis, re-programming those cells to become heart cells. The cells, known as cardiopoietic cells, are then injected back into the patients heart through a minimally invasive procedure, with the aim of repairing damaged tissue and improving heart function and patient clinical outcomes. C-Cure is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA), Cardio3 BioSciences (Mont-Saint-Guibert, Belgium) and Cardiovascular Centre in Aalst (Aalst, Belgium).

About Mayo Clinic Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a non-profit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit http://www.150years.mayoclinic.org ; http://www.mayoclinic.org ; and http://www.newsnetwork.mayoclinic.org . Mayo Clinic has a financial interest in Cardio3 Biosciences.

About Cardio3 BioSciences Cardio3BioSciences is a Belgian leading biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of unmet medical needs. The company was founded in 2007 and is based in the Walloon region of Belgium. Cardio3BioSciences leverages research collaborations in the US and in Europe with Mayo Clinic and the Cardiovascular Centre Aalst, Belgium. The Companys lead product candidate C-Cure is an innovative pharmaceutical product that is being developed for heart failure indication. C-Cure consists of a patients own cells that are harvested from the patients bone marrow and engineered to become new heart muscle. This process is known as Cardiopoiesis. Cardio3BioSciences has also developed C-Cathez, the most technologically advanced injection catheter with superior efficiency of delivery of bio therapeutic agents into the myocardium. Cardio3 BioSciences shares are listed on Euronext Brussels and Euronext Paris under the ticker symbol CARD.

C3BS-CQR-1, C-Cure, C-Cathez, Cardio3 BioSciences and the Cardio3 BioSciences and C-Cathezlogos are trademarks or registered trademarks of Cardio3 BioSciences SA, in Belgium, other countries, or both. Mayo Clinic holds equity in Cardio3 BioSciences as a result of intellectual property licensed to the company. In addition to historical facts or statements of current condition, this press release contains forward-looking statements, which reflect our current expectations and projections about future events, and involve certain known and unknown risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. These forward-looking statements are further qualified by important factors, which could cause actual results to differ materially from those in the forward-looking statements, including timely submission and approval of anticipated regulatory filings; the successful initiation and completion of required Phase III studies; additional clinical results validating the use of adult autologous stem cells to treat heart failure; satisfaction of regulatory and other requirements; and actions of regulatory bodies and other governmental authorities.

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Cardio3 BioSciences Announces the Nomination of Three Co-Principal Investigators for Its CHART-2 Phase III Clinical ...

Released: 10-Nov-2014 9:00 AM EST Source Newsroom: Mayo Clinic Contact Information

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Newswise JACKSONVILLE, Fla. Researchers at Mayo Clinics campus in Jacksonville say they have identified first steps in the origin of pancreatic cancer and that their findings suggest preventive strategies to explore.

In an online issue of Cancer Discovery, the scientists described the molecular steps necessary for acinar cells in the pancreas the cells that release digestive enzymes to become precancerous lesions. Some of these lesions can then morph into cancer.

Pancreatic cancer develops from these lesions, so if we understand how these lesions come about, we may be able to stop the cancer train altogether, says the studys lead investigator, Peter Storz, Ph.D., a cancer biologist.

The need for new treatment and prevention strategies is pressing, Dr. Storz says. Pancreatic cancer is one of the most aggressive human cancers symptoms do not occur until the cancer is well advanced. One-year survival after diagnosis is only 20 percent. It is the fourth leading cause of cancer death in this country.

The scientists studied pancreatic cells with Kras genetic mutations. Kras produces a protein that regulates cell division, and the gene is often mutated in many cancers. More than 95 percent of pancreatic cancer cases have a Kras mutation.

The researchers detailed the steps that led acinar cells with Kras mutations to transform into duct-like cells with stem cell-like properties. Stem cells, which can divide at will, are also often implicated in cancer.

They found that Kras proteins in the acinar cells induce the expression of a molecule, ICAM-1, which attracts macrophages, a specific kind of immune cells. These inflammatory macrophages release a variety of proteins, including some that loosen the structure of the cells, allowing acinar cells to morph into different types of cells. These steps produced the precancerous pancreatic lesions.

We show a direct link between Kras mutations and the inflammatory environment that drive the initiation of pancreatic cancer, Dr. Storz says.

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Mayo Clinic Researchers Identify First Steps in Formation of Pancreatic Cancer