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First stem cell-based approach to treat type 2 diabetes effective in mice

IMAGE:This is an image of macro-encapsulated pancreatic endocrine cells derived from human embryonic stem cells. Devices were harvested at 29 weeks post-transplant and immunofluorescent staining was performed for insulin (red),... view more

A combination of human stem cell transplantation and antidiabetic drugs proved to be highly effective at improving body weight and glucose metabolism in a mouse model of type 2 diabetes. The findings, published March 19th by Stem Cell Reports, could set the stage for clinical trials to test the first stem cell-based approach for insulin replacement in patients with type 2 diabetes.

Type 2 diabetes, which accounts for 90%-95% of the now approaching 400 million cases of diabetes worldwide, is currently treated by oral medication, insulin injections, or both to control blood glucose levels. However, insulin delivery is imprecise, onerous, and often promotes weight gain, while drugs do not work in some patients and may cause gastrointestinal problems or low blood glucose levels, highlighting the strong need for better treatment options.

To address this need, senior study author Timothy Kieffer of the University of British Columbia collaborated with BetaLogics, a division of Janssen Research & Development, LLC, and tested a promising stem cell transplantation approach.

First, they fed mice a high-fat diet to induce obesity, low responsiveness to insulin, and high blood glucose levels--the hallmarks of type 2 diabetes. The mice then received transplants of encapsulated pancreatic progenitor cells derived from human embryonic stem cells. These transplanted cells matured into insulin-secreting beta cells, resulting in improvements in insulin sensitivity and glucose metabolism. Moreover, stem cell transplantation combined with currently available antidiabetic drugs resulted in rapid weight loss in the mice and more significant improvements in glucose metabolism compared with either treatment alone.

Moving forward, the researchers will use their mouse model of type 2 diabetes to test the effectiveness of transplanting more mature insulin-producing cells that could potentially reverse symptoms of diabetes faster and at a lower dose compared to pancreatic progenitor cells.

A similar stem cell-based transplantation approach recently obtained clearance from the US Food and Drug Administration and Health Canada to be tested in patients with type 1 diabetes in phase1/2 clinical trials sponsored by a regenerative medicine company called ViaCyte.

"Success in these clinical trials could pave the way for testing in patients with type 2 diabetes," Kieffer says. "Our hope is that a stem cell-based approach to insulin replacement will ultimately improve glucose control in patients with both type 1 and type 2 diabetes, resulting in healthier, longer lives."

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Dr. Kieffer received financial support from Janssen R&D, LLC, for the research described in this article. The work was also supported by the Canadian Institutes of Health Research (CIHR) Regenerative Medicine and Nanomedicine Initiative, the Stem Cell Network (SCN), the Juvenile Diabetes Research Foundation (JDRF), and Stem Cell Technologies.

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First stem cell-based approach to treat type 2 diabetes effective in mice

Targeted drug doubles progression free survival in Hodgkin lymphoma

A phase 3 trial of brentuximab vedotin (BV), the first new drug for Hodgkin lymphoma in over 30 years, shows that adults with hard-to-treat Hodgkin lymphoma given BV immediately after stem cell transplant survived without the disease progressing for twice as long as those given placebo (43 months vs 24 months).

The findings, published in The Lancet, are potentially practice changing for this young cancer population who have exhausted other treatment options and for whom prognosis is poor.

"No medication available today has had such dramatic results in patients with hard-to-treat Hodgkin lymphoma", says lead author Craig Moskowitz, a Professor of Medicine at Memorial Sloan Kettering Cancer Center, New York, USA.

Hodgkin lymphoma is the most common blood cancer in young adults aged between 15 and 35 years. Most patients are cured with chemotherapy or radiotherapy. However, for patients who relapse, or do not respond to initial therapy, the treatment of choice is usually a combination of high-dose chemotherapy and autologous stem cell transplant (ASCT)--a procedure that uses healthy stem cells from the patient to replace those lost to disease or chemotherapy. While about 50% of patients who undergo this procedure are cured, for the other half treatment is palliative.

BV is an antibody attached to a powerful chemotherapy drug that seeks out cancer cells by targeting the CD30 protein on Hodgkin lymphoma cells. BV sticks to the CD30 protein and delivers chemotherapy directly into the cancer cell to kill it. Recently, BV has been approved for relapsed or refractory Hodgkin lymphoma in 50 countries.

In the AETHERA phase 3 trial, Moskowitz and colleagues aimed to establish whether early treatment with BV after ASCT could prevent disease progression. They randomly assigned 329 patients with Hodgkin lymphoma aged 18 or older who were at high risk of relapse or progression after ASCT to 16 cycles of BV infusions once every 3 weeks or placebo.

At 2 years follow up, the cancer had not progressed at all in 65% of BV patients compared with 45% in the placebo group. "Nearly all of these patients who are progression free at 2 years are likely to be cured since relapse 2 years after a transplant is unlikely", explains Dr Moskowitz.

BV was generally well tolerated. The most common side effects were peripheral neuropathy (numbness or pain in the extremities due to nerve damage; 67% BV vs 13% placebo) and neutropenia (low white blood count; 35% vs 12%).

According to Dr Moskowitz, "The bottom line is that BV is a very effective drug in poor risk Hodgkin lymphoma and it spares patients from the harmful effects of further traditional chemotherapy by breaking down inside the cell resulting in less toxicity."

Writing in a linked Comment, Professor Andreas Engert from the University Hospital of Cologne in Germany discusses how best to define which patients are at high risk of relapse and should be treated with BV. He writes, "AETHERA is a positive study establishing a promising new treatment approach for patients with Hodgkin's lymphoma at high risk for relapse. However, with a progression-free survival of about 50% at 24 months in the placebo group, whether this patient population is indeed high risk could be debated...An international consortium is currently reassessing the effect of risk factors in patients with relapsed Hodgkin's lymphoma to define a high-risk patient population in need of consolidation treatment. We look forward to a better definition of patients with relapsed Hodgkin's lymphoma who should receive consolidation treatment with brentuximab vedotin.

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Targeted drug doubles progression free survival in Hodgkin lymphoma

Study Shows Liposuction Byproduct Could Lead to ED Cure

Durham, NC (PRWEB) March 19, 2015

A new study appearing in STEM CELLS Translational Medicine has moved science one step closer to finding a simple treatment for erectile dysfunction (ED) after prostate cancer surgery, eschewing the usual pharmaceutical drug route with potential for harmful side effects, in favor of stem cell therapy that can help the body regenerate.

The study, conducted in rats, compares the effectiveness of using a byproduct of liposuction uncultured stromal vascular fraction (SVF) with adipose-derived stem cells (ADSCs) cultured in the lab to treat ED caused by injury to the cavernous nerve (CN). This nerve, which facilities erection, is sometimes injured during a radical prostatectomy to treat prostate cancer.

ADSCs are harvested from fat and are an attractive source of stem cells for several reasons: They are abundant and can be easily obtained using minimally invasive liposuction. Also, they have characteristics similar to bone marrow-derived stem cells in terms of self-renewal and multipotency. Furthermore, ADSCs retain their ability to divide and grow longer than bone marrow-derived stem cells, which may be beneficial in treating chronic conditions.

On the other hand, cultured ADSCs have limitations, including the cost and time of culturing them, the potential for contamination, changes in cell characteristics during culturing procedures, and their tendency to sometimes form tumors. To avoid these risks, uncultured SVF has emerged as an easier and safer way to use stem and progenitor cells (which are further along in the differentiation process) derived from adipose tissue. SVF comes from the disposable byproduct of liposuction.

However, no study had yet reported side-by-side comparisons of uncultured SVF and cultured ADSCs in treating ED. That was the objective of this study, led by Dalsan You, M.D., Ph.D., and Choung-Soo Kim, M.D., Ph.D., and their colleagues at the Asan Medical Center and University of Ulsan College of Medicine in Seoul, Korea. They tested the cells using 40 rats with and without injured CNs. One group of animals was injected with cultured ADSCs; one received uncultured SVF, and a control group received no stem cells. Four weeks later, both sources of stem cells had significantly improved the animals erection function over the control group. Also, both stem cell types significantly increased the number of nNOS-positive nerve fibers, suggesting that they stimulated nerve regeneration.

However, Dr. Kim said, the cells coming from uncultured SVF outperformed the cultured ADSCs in terms of smooth muscle/collagen ratio and endothelial cell content in the blood vessels, which are also important factors in repairing ED.

Further research is now ongoing to determine the optimal protocol for cellular therapy of ED following CN injury, Dr. You added. We want to follow the progress of the animals over the long term and also we want to see what happens with multiple stem cell injections, rather than just the one given in this study.

This first study to compare two types of cells derived from fat tissue in a rat model of erectile dysfunction after prostate cancer surgery is an important step in identifying effective new treatments for this condition, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Study Shows Liposuction Byproduct Could Lead to ED Cure

UM stem cell research on heart may go national

Written by Lidia Dinkova on March 18, 2015

University of Miami stem cell research on generating healthy heart tissue in heart attack survivors is on track to be tested across the US.

The National Heart, Lung and Blood Institute, part of federal medical research arm the National Institutes of Health, is to fund the $8 million cost if the trial wins necessary approvals.

The trial, the first of this research in humans, is a step toward restoring full heart function in heart attack survivors.

The research developed at the UM Miller School of Medicines Interdisciplinary Stem Cell Institute is on combining two types of stem cells to generate healthy heart tissue in heart attack survivors. Scientists have in the past studied using one type of stem cell at a time, a method thats worked OK, said Dr. Joshua Hare, founding director of the UM stem cell institute.

But UM research shows that combining two types of stem cells expedites healing and regeneration of healthy heart muscle.

We could remove twice the scar tissue than with either cell alone, Dr. Hare said. We had some scientific information that they actually interacted and worked together, so we tested that. It worked.

Researchers combined mesenchymal stem cells, usually generated from human bone marrow, and cardiac stem cells, isolated from a mammals heart.

Stem cells are cells that havent matured to specialize to work in a particular part of the body, such as the heart. Because these cells are in a way nascent, they have the potential to become specialized for a particular body function.

Doctors have been using stem cells to regenerate lost tissue from bones to heart muscle. The mesenchymal and cardiac stem cells each work well in generating healthy heart tissue in heart attack survivors, Dr. Hare said. Combining them expedites the process, according to the UM research.

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UM stem cell research on heart may go national

Boston Stem Cell Biotech Start-up Asymmetrex Will Present Essential Technologies for Stem Cell Medical Engineering at …

Boston, MA (PRWEB) March 18, 2015

In the vast flow of new scientific research, discoveries, and information, it is not uncommon for important scientific advances to go unappreciated, or even just unnoticed, for surprisingly long periods of time. The Boston stem cell medicine technology start-up company, Asymmetrex is working to make sure that its growing portfolio of adult tissue stem cell technology patents obtains wide notice, appreciation, and investment.

In late 2014, the company started a digital media campaign to achieve greater visibility for its patented technologies that address the major barriers to greater progress in stem cell medicine. These include technologies for identifying, counting, and mass-producing adult tissue stem cells. The two presentations scheduled for the 5th World Congress on Cell and Stem Cell Research in Chicago continue Asymmetrexs efforts to better inform medical, research, and industrial communities focused on advancing stem cell medicine of the companys vision for implementation of its unique technologies.

Asymmetrex holds patents for the only method described for routine production of natural human tissue stem cells that retain their normal function. The company also holds patents for biomarkers that can be used to count tissue stem cells for the first time. The companys most recently developed technology was invented with computer-simulation leader, AlphaSTAR Corporation. In partnership, the two companies created a first-of-its-kind method for monitoring adult tissue stem cell number and function for any human tissue that can be cultured. This advance is the basis for the two companies AlphaSTEM technology for detecting adult tissue stem cell-toxic drug candidates before conventional preclinical testing in animals or clinical trials. Asymmetrex and AlphaSTAR plan to market the new technology to pharmaceutical companies. The implementation of AlphaSTEM technology would accelerate drug development and reduce adverse drug events for volunteers and patients. At full capacity use, AlphaSTEM could reduce U.S. drug development costs by $4-5 billion each year.

About Asymmetrex (http://asymmetrex.com/)

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrexs founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrexs focus is employing its technological advantages to develop facile methods for monitoring adult stem cell number and function in clinically important human tissues.

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Boston Stem Cell Biotech Start-up Asymmetrex Will Present Essential Technologies for Stem Cell Medical Engineering at ...

A Single-Cell Breakthrough: newly developed technology dissects properties of single stem cells

The human gut is a remarkable thing. Every week the intestines regenerate a new lining, sloughing off the equivalent surface area of a studio apartment and refurbishing it with new cells. For decades, researchers have known that the party responsible for this extreme makeover were intestinal stem cells, but it wasn't until this year that Scott Magness, PhD, associate professor of medicine, cell biology and physiology, and biomedical engineering, figured out a way to isolate and grow thousands of these elusive cells in the laboratory at one time. This high throughput technological advance now promises to give scientists the ability to study stem cell biology and explore the origins of inflammatory bowel disease, intestinal cancers, and other gastrointestinal disorders.

But it didn't come easy.

One Step Forward . . .

When Magness and his team first began working with intestinal stem cells some years ago, they quickly found themselves behind the eight ball. Their first technique involved using a specific molecule or marker on the surface of stem cells to make sure they could distinguish stem cells from other intestinal cells. Then Magness's team would fish out only the stem cells from intestinal tissues and grow the cells in Petri dishes. But there was a problem. Even though all of the isolated cells had the same stem cell marker, only one out of every 100 could "self-renew" and differentiate into specialized cells like a typical stem cell should. (Stem cells spawn cells that have specialized functions necessary for any organ to work properly.)

"The question was: why didn't the 99 others behave like stem cells?" Magness said. "We thought it was probably because they're not all the same, just like everybody named Judy doesn't look the same. There are all kinds of differences, and we've been presuming that these cells are all the same based on this one name, this one molecular marker. That's been a problem. But the only way to solve it so we could study these cells was to look at intestinal stem cells at the single cell level, which had never been done before."

Magness is among a growing contingent of researchers who recognize that many of the biological processes underlying health and disease are driven by a tiny fraction of the 37 trillion cells that make up the human body. Individual cells can replenish aging tissues, develop drug resistance, and become vehicles for viral infections. And yet the effects of these singular actors are often missed in biological studies that focus on pooled populations of thousands of seemingly "identical" cells.

Distinguishing between the true intestinal stem cells and their cellular look-a-likes would require isolating tens of thousands of stem cells and tracking the behavior of each individual cell over time. But Magness had no idea how to accomplish that feat. Enter Nancy Allbritton, PhD, chair of the UNC/NCSU Joint Department of Biomedical Engineering. The two professors met one day to discuss Magness joining the biomedical engineering department as an adjunct faculty member. And they did discuss it. And Magness did join. But the meeting quickly turned into collaboration. One of Allbritton's areas of expertise is microfabrication -- the ability to squeeze large devices into very small footprints. During their meeting, Allbritton showed Magness her latest creation, a device smaller than a credit card dotted with 15,000 tiny wells for culturing cells.

"It was like a light bulb went off, and I realized I was looking at the answer to a billion of our problems," Magness said.

Micro Magic

Each microwell is as thick as a strand of hair. By placing individual stem cells into the microwells, Magness and postdoctoral fellow Adam Gracz, PhD, could watch the cells grow into fully developed tissue structures known as mini-guts. Each microwell could be stamped with a specific address, which would allow researchers to track stem cells that were behaving as expected and those that weren't.

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A Single-Cell Breakthrough: newly developed technology dissects properties of single stem cells

BrainStorm Cell Therapeutics to Present at 3rd Annual Regen Med Investor Day on March 25 in New York

HACKENSACK, N.J.and PETACH TIKVAH, Israel, March 18, 2015 /PRNewswire/ --BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell technologies for neurodegenerative diseases, announced today that CEO Tony Fiorino, MD, PhD, will present at the 3rd Annual Regen Med Investor Day to be held Wednesday, March 25, 2015 in New York City.

Organized by the Alliance for Regenerative Medicine (ARM) and co-hosted with Piper Jaffray, this one-day investor meeting provides institutional, strategic and venture investors with unique insight into the financing hypothesis for advanced therapies-based treatment and tools. The program includes clinical and commercial experts who are on-hand to address specific questions regarding the outlook for these products, as well as offer insight into how advanced therapies could impact the standard of care in key therapeutic areas. In addition to presentations by more than 30 leading companies from across the globe, the event includes dynamic, interactive panels featuring research analysts covering the space, key clinical opinion leaders and top company CEOs. These discussions will explore themes specific to cell and gene therapy such as commercialization, market access and pricing for breakthrough technologies, gene therapy delivery and upcoming milestones in the adoptive T-cell therapy space.

The following are specific details regarding BrainStorm's presentation:

Event:

ARM's Regen Med Investor Day

Date:

March 25, 2015

Time:

4:20 PM EST

Location:

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BrainStorm Cell Therapeutics to Present at 3rd Annual Regen Med Investor Day on March 25 in New York

A single-cell breakthrough

9 hours ago by Marla Vacek Broadfoot A jelly fish-green fluorescent gene marks stem cells and other proliferating primitive cells of an intestine-like structure. The central lumen hollow space is stained red. Credit: Magness Lab

The human gut is a remarkable thing. Every week the intestines regenerate a new lining, sloughing off the equivalent surface area of a studio apartment and refurbishing it with new cells. For decades, researchers have known that the party responsible for this extreme makeover were intestinal stem cells, but it wasn't until this year that Scott Magness, PhD, associate professor of medicine, cell biology and physiology, and biomedical engineering, figured out a way to isolate and grow thousands of these elusive cells in the laboratory at one time. This high throughput technological advance now promises to give scientists the ability to study stem cell biology and explore the origins of inflammatory bowel disease, intestinal cancers, and other gastrointestinal disorders.

But it didn't come easy.

One step forward

When Magness and his team first began working with intestinal stem cells some years ago, they quickly found themselves behind the eight ball. Their first technique involved using a specific molecule or marker on the surface of stem cells to make sure they could distinguish stem cells from other intestinal cells.

Then Magness's team would fish out only the stem cells from intestinal tissues and grow the cells in Petri dishes. But there was a problem. Even though all of the isolated cells had the same stem cell marker, only one out of every 100 could "self-renew" and differentiate into specialized cells like a typical stem cell should. (Stem cells spawn cells that have specialized functions necessary for any organ to work properly.)

"The question was: why didn't the 99 others behave like stem cells?" Magness said. "We thought it was probably because they're not all the same, just like everybody named Judy doesn't look the same. There are all kinds of differences, and we've been presuming that these cells are all the same based on this one name, this one molecular marker. That's been a problem. But the only way to solve it so we could study these cells was to look at intestinal stem cells at the single cell level, which had never been done before."

Magness is among a growing contingent of researchers who recognize that many of the biological processes underlying health and disease are driven by a tiny fraction of the 37 trillion cells that make up the human body. Individual cells can replenish aging tissues, develop drug resistance, and become vehicles for viral infections. And yet the effects of these singular actors are often missed in biological studies that focus on pooled populations of thousands of seemingly "identical" cells.

Distinguishing between the true intestinal stem cells and their cellular look-a-likes would require isolating tens of thousands of stem cells and tracking the behavior of each individual cell over time. But Magness had no idea how to accomplish that feat. Enter Nancy Allbritton, PhD, chair of the UNC/NCSU Joint Department of Biomedical Engineering. The two professors met one day to discuss Magness joining the biomedical engineering department as an adjunct faculty member. And they did discuss it. And Magness did join. But the meeting quickly turned into collaboration.

One of Allbritton's areas of expertise is microfabrication the ability to squeeze large devices into very small footprints. During their meeting, Allbritton showed Magness her latest creation, a device smaller than a credit card dotted with 15,000 tiny wells for culturing cells.

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A single-cell breakthrough

Beware stem cell therapy for lung disease

Clinics in other countries for some time have promised dramatic results in the treatment of lung disease, primarily emphysema, through the use of autologous stem cells obtained from the patient. The stem cells are extracted from adipose (fat) tissue, treated and then injected into the patient. The cells then supposedly go to work regenerating and replacing the damaged lung tissue.

Several of this type of clinic are now popping up in parts of the United States, mostly in California and Florida. Their advertisements are filled with testimonials from patients, extolling the virtues of the treatments. The treatments are quite expensive, and would be an absolute godsend for the 30 million Americans who suffer from some stage of Chronic Obstructive Pulmonary Disease (COPD). If they worked.

Trouble is, none of these clinics or their treatments are approved by the FDA, and the only proof of their effectiveness is anecdotal, coming from selected customers.

Anyone with a chronic, progressive disease, such as COPD, will usually find themselves in a situation of desperation, eager to embrace any promises of a cure. I have been there, and it is a terrible situation.

Sadly, further research shows that institutions that are working on stem cell therapy for lungs unanimously agree that the successful regeneration of human lung tissue is likely decades away. Dr. Hatch, a British researcher, states that he may be able to announce success in about 20 years. Boston University states that stem cell treatment for lungs may be available for our grandchildren or great-grandchildren.

Even the Center for Regenerative Medicine at Wake Forest, which has successfully built working bladders and other of the simpler internal organs, states that we are likely 20 years away from creating a lung.

There have always been those who would separate us from our money with promises of cures of everything from cancer to male pattern baldness. Please beware.

Jim Nelson is a former Glenwood Springs resident who works with regional and national cardiovascular and lung organizations.

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Beware stem cell therapy for lung disease