Weakness of leukaemic stem cells discovered

05.08.2014 - (idw) Goethe-Universitt Frankfurt am Main

Only one out of every two adult patients survive acute myeloid leukaemia (AML). It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. Now a team of Frankfurt-based researchers has discovered, that these cells do have a weakness: 5-LO inhibitors eliminate cells in culture and mouse models. FRANKFURT. Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research", they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.

5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jrgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukaemia mouse models.

"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells", Prof. Maier continued.

Information PD Dr. Martin Ruthardt, Haematology/Medical Clinic II, Tel. +49/ 69/63015338, email: ruthardt@em.uni-frankfurt.de or Prof. Dr. Thorsten Jrgen Maier, Institute for Pharmaceutical Chemistry, Riedberg Campus, Tel.: +49/69/7982-934, email: maier@pharmchem.uni-frankfurt.de.

The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day. Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities.

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Weakness of leukaemic stem cells discovered

Weakness of leukemic stem cells discovered

PUBLIC RELEASE DATE:

4-Aug-2014

Contact: Anke Sauter 49-069-798-12498 Goethe University Frankfurt

FRANKFURT. Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research", they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.

5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jrgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukaemia mouse models.

"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells." Prof. Maier continued.

###

Publication:

Roos et al.: 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia, in Cancer Research Volume (2014), Published OnlineFirst July 31, 2014; doi:10.1158/0008-5472.CAN-13-3012

Information PD Dr. Martin Ruthardt, Haematology/Medical Clinic II, Tel. +49/ 69/6301-5338, email: ruthardt@em.uni-frankfurt.de or Prof. Dr. Thorsten Jrgen Maier, Institute for Pharmaceutical Chemistry, Riedberg Campus, Tel.: +49/69/7982-934, email: maier@pharmchem.uni-frankfurt.de.

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Weakness of leukemic stem cells discovered

Stem Cell Therapy, Stem Cell Research, Stem Cell Treatments

Welcome to the Silicon Valley Stem Cell Treatment Center, and affiliate of the California Stem Cell Treatment Center. At our state of the art clinic we are using cutting edge advanced techniques and the latest innovative technology to improve the health and well being of our patients. At Silicon Valley Stem Cell Treatment Center, we provide care for people suffering from diseases that may have limited treatment options and may respond to stem cell based regenerative treatment. The Silicon Valley Stem Cell Treatment Center emphasizes quality and our well trained physician is highly committed to clinical research and the advancement of regenerative medicine.

The California Stem Cell Treatment specialists who trained our physician, have been nationally recognized for working with autologous (your own) adipose derived stem cells providing investigational therapy to patients with various inflammatory and/or degenerative conditions. Our Centers utilize a fat transfer technology to isolate and implant the patient's own stem cells from a small quantity of fat harvested by liposuction on the same day. Using technology developed in South Korea, our group has developed an in office procedure to isolate this cellular medium called the Stromal Vascular Fraction or SVF which is very rich in stem cells. Our founders have also worked in conjunction with a number of international organizations and physicians of great expertise to help develop our protocols for procedures. In 2012, the Cell Surgical Network (CSN) was formed, of which we are an affiliate, to provide the same high level quality controlled investigational therapy nationwide and beyond. Under our IRB (Institutional Review Board) approved protocol, we in Silicon Valley are now also able to provide fat derived stem cell procedures on an investigational basis. Modeled after the California Stem Cell Treatment Center, we've formed a multidisciplinary team to evaluate patients with a variety of conditions often responsive to Stem Cell therapy. All affiliate members in the CSN, including our clinic will contribute to the California Centers IRB approved investigation. Patients who seek care at the Silicon Valley Stem Cell Treatment Center will be evaluated by one of our physicians and given our honest opinion as to the potential benefits and risks of stem cell therapy for their presenting condition.

California Stem Cell Treatment Center was founded in 2010 for the investigational use of stem cells procedures for degenerative conditions. California Stem Cell Treatment Center employs a clinical research coordinator to protect our valuable data, as our vision is to perfect our treatments and ultimately teach them to others.

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Stem Cell Therapy, Stem Cell Research, Stem Cell Treatments

Gift from Bacardi family will help Mayo Clinic researchers in Jacksonville close in on 'the future of medicine'

The future of medicine is regenerative medicine.

Thats a view shared by Thomas Gonwa, associate director of the Mayo Clinic Center for Regenerative Medicine in Jacksonville, and by Jorge and Leslie Bacardi.

Regenerative medicine will be the cutting-edge medicine of the 21st century, Gonwa says.

We think it is the most important thing happening in medicine, Leslie Bacardi said.

Now the Bacardis, who live in Nassau in the Bahamas, have given what Mayo Clinic officials call a substantial gift to fund ongoing research and clinical trials in regenerative medicine at the Mayo Clinic in Jacksonville.

Jorge Bacardi, part of the family that has been making rum and other spirits for 150 years, declined to specify the amount of the gift. Were not people who boast about the amount we give, he said.

Its an amount that should be sufficient to fund the ongoing research into regenerative medicine in Jacksonville, he said.

Doctors at the Mayo Clinic both in Jacksonville and in Rochester, Minn., now envision a future in which new organs can be grown for patients, using their own cells, and a time when the injection of stem cells can be used to repair a damaged organ.

Last year, Tim Nelson, a physician with the Center for Regenerative Medicine in Rochester, removed tissue from the arm of ABC Nightline reporter Bill Weir and created what Weir called a tiny piece of my cardiac tissue that had dramatically formed into the shape of a heart a pumping, three-dimensional glimpse into a future when this kind of cell could theoretically be injected into a heart-attack victim or a diseased child and literally mend the person from within.

That, to us, was just mind-boggling, Leslie Bacardi said. ... Regenerative medicine is for us an investment in our future and the future of medicine. It may take a while to reap any benefits, but when those benefits do come, it will make the investment seem small.

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Gift from Bacardi family will help Mayo Clinic researchers in Jacksonville close in on 'the future of medicine'

St. Olaf student awarded Harvard Stem Cell Institute internship

July 28, 2014

As part of her Harvard Stem Cell Institute internship, St. Olaf student Alexa Roemmich 15 is working to grow adult mouse inner ear stem cells in a laboratory dish something that has never been done before.

St. Olaf College student Alexa Roemmich 15 is one of 40 undergraduate students from around the world selected to participate in the 2014 Harvard Stem Cell Institute (HSCI) Internship Program, which provides participants with a challenging summer research experience in a cutting-edge stem cell science laboratory.

Roemmich is spending 10 weeks in the Massachusetts Eye and Ear Infirmary laboratory of faculty member Zheng-Yi Chen, known for his research on age-related and noise-induced hearing loss.

Roemmichs project this summer is to grow adult mouse inner ear stem cells in a laboratory dish something that has never been done before with the goal of persuading these cells to become the sound-converting cells that are lost in an aging or damaged ear.

Im working on a project that no one has succeeded at before, Roemmich says. Its very exciting. Im able to experience the scientific process in a very real way my results are unknown, and any new result is something that can be learned.

Ive had excellent opportunities at St. Olaf, and also from my summers at the University of North Dakota and the Mayo Clinic, that prepared me to design and carry out multi-week experiments, she adds. I cannot wait to continue my scientific journey in graduate school and beyond.

Over the course of the HSCI program, interns participate in a stem cell seminar series, a career pathways presentation, and a weekly stem cell companion course. They present their summer research findings, both orally and in poster format, at an end-of-program symposium.

This program represents an exciting opportunity for undergraduates to gain hands-on experience in stem cell research while working in an HSCI laboratory under the supervision of an experienced researcher, says HSCI Internship Program Co-Director M. William Lensch.

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St. Olaf student awarded Harvard Stem Cell Institute internship

Large Study of Stem Cells for Autism Draws Criticism

Experts say a $15 million trial to explore stem cells from cord blood for treating autism is premature.

Cold comfort: Researchers are trying to find out whether stem cells taken from frozen cord blood can improve autism symptoms. Credit:Tbsdy lives via Wikimedia Commons

A team at Duke University in Durham, North Carolina, is set to launch a $40 million clinical trial to explore stem cells from umbilical cord blood as a treatment for autism. But experts caution that the trial is premature.

A $15 million grant from the Marcus Foundation, a philanthropic funding organization based in Atlanta, will bankroll the first two years of the five-year trial, which also plans to test stem cell therapy for stroke and cerebral palsy. The autism arm of the trial aims to enroll 390 children and adults.

Joanne Kurtzberg, the trials lead investigator, has extensive experience studying the effectiveness of cord blood transplants for treating various disorders, such as leukemia and sickle cell anemia. Most recently, she showed that cord blood transplants can improve the odds of survival for babies deprived of oxygen at birth. A randomized trial of the approach for this condition is underway.

To really sort out if [stem] cells can treat these children, we need to do randomized, controlled trials that are well designed and well controlled, and thats what we intend to do, says Kurtzberg, professor of pediatrics and pathology at Duke. We firmly believe we should be moving ahead in the clinic.

Early animal studies have shown that stem cells isolated from umbilical cord blood can stimulate cells in the spinal cord to regrow their myelin layers, and in doing so help restore connections with surrounding cells. Autism is thought to result from impaired connectivity in the brain. Because of this, some groups of children with the disorder may benefit from a stem cell transplant, Kurtzberg says.

But others are skeptical of the approach. Autism is a complex disorder with many possible causes. Also, its unclear how stem cells derived from cord blood can improve connections in the brain. Given these important caveats, its too soon to conduct a test of this scale and investment, some experts say.

Its probably premature to run large trials without evidence that they have a therapeutic effect that [we] understand, cautions Arnold Kriegstein, director of the Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, San Francisco.

Pilot trials In June, Kurtzberg launched the first phase of the trial, with 20 children between 2 and 5 years of age. Her team plans to infuse the children with a single dose of their own cord blood cells, banked at birth and preserved by freezing.

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Large Study of Stem Cells for Autism Draws Criticism

No extra mutations in modified stem cells

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world.

He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease.

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No extra mutations in modified stem cells

No Extra Mutations in Modified Stem Cells, Study Finds

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Newswise LA JOLLA-The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise--the hope of fixing disease-causing genes in humans, for example--as well as questions and safety concerns. Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells--either for research purposes or to fix a genetic mutation for therapeutic purposes--they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one. Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world. He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes--such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro--including gene editing--might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease. They edited the genes of some cells using one of two HDAdV designs, edited others using one of two TALEN proteins, and kept the rest of the cells in culture without editing them. Then, they fully sequenced the entire genome of each cell from the four edits and control experiment.

While all of the cells gained a low level of random gene mutations during the experiments, the cells that had undergone gene-editing--whether through HDAdV- or TALEN-based approaches--had no more mutations than the cells kept in culture.

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No Extra Mutations in Modified Stem Cells, Study Finds

MediVet America Victorious in Vet-Stem Litigation

Nicholasville, KY (PRWEB) July 07, 2014

MediVet America Victorious in Vet-Stem Litigation

MediVet America, LLC is pleased to announce to its current and future customers a recent settlement with Vet-Stem, Inc. This decision, resulting from a lawsuit (MediVet America vs. Vet-Stem, Inc. Case # 13CV0498-WVG, United States District Court, So. District of California) was brought against Veterinary regenerative market competitor Vet-Stem (Poway, CA) and as of close of business July 1st 2014, brings an end to the dissemination of alleged misleading information by Vet-Stem.

The decision extends vindication to MediVet America as it relates to damaging and unsubstantiated claims against its patented regenerative medicine therapies for the large and small animal market. To date, over 10,000 animals have been treated with MediVets flagship product offering, adipose derived stem cell therapy. Through recent scientific efforts and support from the University of Kentucky College of Medicine as well as Nexellcom Biosciences (Lawrence, MA), MediVets system and protocols were independently validated. These studies can be found on the companys website http://www.medivet-america.com/references as well as in the prestigious peer reviewed Journal of Fluorescence, Automated Enumeration and Viability Measurement of Canine Stromal Vascular Fraction Cells Using Fluorescence-Based Image Cytometry Method. J.Fluoresc. 2014, Apr 17. Chan LL, Cohen DA, Kuksin D, Paradis BD, Qiu J.

Today, MediVet is pleased to announce a favorable out of court settlement in the case the company brought against Vet-Stem. This legal actionable measure to protect the MediVet brand was taken in response to false claims allegedly made in a 2013 research project from INCELL corporation. The research project, funded by Vet-Stem, was aimed at discrediting the MediVet technology and to disrupt MediVets growing market share in the Veterinary regenerative medicine space.

MediVet CEO, Jeremy Delk was pleased to put the matter to rest. This is a true victory, and extends credence once again to our message, that our mission is to continue to offer innovative solutions based in science to the Veterinary market. While the terms of the settlement are confidential, we can say that we are pleased, and this substantial six figure settlement reiterates we will not allow our loyal customers and future customers to be misled for commercially driven purposes. Furthermore, as leaders in this market it is our duty to continue to offer innovation and bring answers to an ever evolving technology. We will continue to innovate, and protect the right to do so in order to bring the gold standard in Regenerative Medicine to the progressive customers we serve today, tomorrow and in the future irrespective of the legal costs to do so.

MediVet America:

Based right outside of Lexington, KY, MediVet is the global leader in Veterinary regenerative medicine. As of Jan 1, 2014 MediVet is a part of Medical Australia, a strategic move to secure resources for future research and development projects. Since 2009 MediVet has offered a wide variety of autologous healing modalities for the equine and small animal market. To date over 1000 Veterinarians are certified to practice in-clinic adipose derived stem cell treatments.

For additional information, please email MediVet America at info@medivet-america.com or feel free to call us at 859-885-7111.

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MediVet America Victorious in Vet-Stem Litigation

New method to grow zebrafish embryonic stem cells

Date:

June 30, 2014

Source:

Mary Ann Liebert, Inc., Publishers

Summary:

Zebrafish, a model organism that plays an important role in biological research and the discovery and development of new drugs and cell-based therapies, can form embryonic stem cells (ESCs). For the first time, researchers report the ability to maintain zebrafish-derived ESCs for more than two years without the need to grow them on a feeder cell layer.

Zebrafish, a model organism that plays an important role in biological research and the discovery and development of new drugs and cell-based therapies, can form embryonic stem cells (ESCs). For the first time, researchers report the ability to maintain zebrafish-derived ESCs for more than two years without the need to grow them on a feeder cell layer, in a study published in Zebrafish, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

Ho Sing Yee and coauthors from the Malaysian Ministry of Science, Technology and Innovation (Pulau Pinang), Universiti Sains Malaysia (Penang), and National University of Singapore describe the approach they used to be able to maintain zebrafish stem cells in culture and in an undifferentiated state for long periods of time. The ability to establish and grow the zebrafish ESCs without having a feeder layer of cells to support them simplifies their use and could expand their utility. In the article "Derivation and Long-Term Culture of an Embryonic Stem Cell-Like Line from Zebrafish Blastomeres Under Feeder-Free Condition," the authors show that the ESCs retain the morphology, properties, and ability to differentiate into a variety of cell types that is characteristic of ESCs, and were used to generate offspring after transmission through the germline.

"By addressing a major technical bottleneck in the field, this new culture system enables an array of exciting cellular and molecular genetic manipulations for the zebrafish," says Stephen Ekker, PhD, Editor-in-Chief of Zebrafish and Professor of Medicine at Mayo Clinic, Rochester, MN.

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New method to grow zebrafish embryonic stem cells