Embryonic stem cells offer new treatment for multiple sclerosis

PUBLIC RELEASE DATE:

16-Jun-2014

Contact: Colin Poitras colin.poitras@uconn.edu 860-486-4656 University of Connecticut

Scientists in the University of Connecticut's Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.

The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models and offered better treatment results than stem cells derived from human adult bone marrow.

The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.

"The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside," says Professor Marc Lalande, director of the UConn's Stem Cell Institute.

The research was supported by a $1.13 million group grant from the state of Connecticut's Stem Cell Research Program that was awarded to ImStem and Professor Pachter's lab.

"Connecticut's investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research," says Gov. Dannel P. Malloy. "This new study moves us one step closer to a stem cell-based clinical product that could improve people's lives."

The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.

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Embryonic stem cells offer new treatment for multiple sclerosis

Microenvironment of hematopoietic stem cells can be a target for myeloproliferative disorders

The discovery of a new therapeutic target for certain kinds of myeloproliferative disease is, without doubt, good news. This is precisely the discovery made by the Stem Cell Physiopathology group at the CNIC (the Spanish National Cardiovascular Research Center), led by Dr. Simn Mndez-Ferrer. The team has shown that the microenvironment that controls hematopoietic stem cells can be targeted for the treatment of a set of disorders called myeloproliferative neoplasias, the most prominent of which are chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myelogenous leukemia (CML).

The findings, published today in Nature, demonstrate that these myeloproliferative neoplasias only appear after damage to the microenvironment that sustains and controls the hematopoietic stem cells -- the cells that produce the cells of the blood and the immune system. Protecting this microenvironment, or niche, has thus emerged as a new route for the treatment of these diseases, for which there is currently no fully effective treatment.

"In normal conditions, the microenvironment is able to control the proliferation, differentiation and migration of the hematopoietic stem cell. A specific genetic mutation in these cells results in inflammatory injury to the microenvironment and this control breaks down. What our work shows is that this damage can be prevented or reversed by treatments that target the niche," explained Dr. Mndez-Ferrer.

Indeed, the same team of researchers has demonstrated the efficacy of a possible new treatment, which has been patented through the CNIC. The treatment involves an innovative use of clinically approved treatments for other diseases, so that, according to the authors, "it shouldn't be associated with adverse side effects." The new treatment route has been tested in animals and has received financial backing for a multicenter phase II clinical trial. "This study has a very strong translational and clinical potential," emphasized study first author Dr. Lorena Arranz, who added that "current treatment for myeloproliferative neoplasias is largely symptomatic and directed at preventing thrombosis and fatal cardiovascular events."

The only real cure available today is a bone marrow transplant, which is not advisable in patients over 50 years old. "This makes it important to identify new therapeutic targets for the development of effective treatments," the investigators conclude.

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The above story is based on materials provided by Centro Nacional de Investigaciones Cardiovasculares. Note: Materials may be edited for content and length.

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Microenvironment of hematopoietic stem cells can be a target for myeloproliferative disorders

Pushing cells towards a higher pluripotency state

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Stem cells have the unique ability to become any type of cell in the body. Given this, the possibility that they can be cultured and engineered in the laboratory makes them an attractive option for regenerative medicine. However, some conditions that are commonly used for culturing human stem cells have the potential to introduce contaminants, thus rendering the cells unusable for clinical use. These conditions cannot be avoided, however, as they help maintain the pluripotency of the stem cells.

In a study published in Scientific Reports, a group from the RIKEN Center for Life Science Technologies in Japan has gained new insight into the role of CCL2, a chemokine known to be involved in the immune response, in the enhancement of stem cell pluripotency. In the study, the researchers replaced basic fibroblast growth factor (bFGF), a critical component of human stem cell culture, with CCL2 and studied its effect. The work showed that CCL2 used as a replacement for bFGF activated the JAK/STAT pathway, which is known to be involved in the immune response and maintenance of mouse pluripotent stem cells. In addition, the cells cultured with CCL2 demonstrated a higher tendency of colony attachment, high efficiency of cellular differentiation, and hints of X chromosome reactivation in female cells, all markers of pluripotency.

To understand the global effects of CCL2, the researchers compared the transcriptome of stem cells cultured with CCL2 and those with bFGF. They found that stem cells cultured with CCL2 had higher expression of genes related to the hypoxic response, such as HIF2A (EPAS1). The study opens up avenues for further exploring the relationship between cellular stress, such as hypoxia, and the enhancement of pluripotency in cells. Yuki Hasegawa of CLST, who led the study, says, "Among the differentially expressed genes, we found out that the most significantly differentially expressed ones were those related to hypoxic responses, and hypoxia is known to be important in the progression of tumors and the maintenance of pluripotency. These results could potentially contribute to greater consistency of human induced pluripotent stem cells (iPSCs), which are important both for regenerative medicine and for research into diseases processes."

As a way to apply CCL2 towards the culturing of human iPSCs with more consistent quality, the researchers developed dishes coated with CCL2 and LIF protein beads. This allowed stem cells to be cultured in a feeder-free condition, preventing the risk that viruses or other contaminants could be transmitted to the stem cells. While the exact mechanisms of how CCL2 enhances pluripotency has yet to be elucidated, this work highlights the usefulness of CCL2 in stem cell culture.

Explore further: Soft substrates may promote the production of induced pluripotent stem cells

Journal reference: Scientific Reports

Provided by RIKEN

A protein that helps maintain mouse stem cell pluripotency has been identified by researchers at the RIKEN Omics Science Center. The finding, published in the August issue of Stem Cells (first published online ...

Converting adult cells into stem cells that can develop into other types of specialized cells is one of the most active areas of medical research, holding great promise for the treatment of disease and repair ...

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Pushing cells towards a higher pluripotency state

Cancer survivor follows his dream of launching a craft beer business

JEHAD HATU has had chemotherapy, a stem cell transplant and a 13-hour operation during his two-year cancer fight.

But the 26-year-old says living with stage three testicular cancer has not left him disheartened. Instead, it has given him the push to follow his dreams of launching a craft beer business. When the Evening times first told Jehad's story in November 2012, he had just completed a course of chemotherapy and was preparing for surgery.

However, the former bar and restaurant worker's health deteriorated and medics feared he would never recover.

Jehad, who lives in Glasgow's South Side, said: "It's just one of those things. Sometimes life throws you an unexpected curveball."

After four months of lower back-ache, he was diagnosed in August 2012 with the illness, which had spread to his lymph nodes, his liver, his intestines and his lungs . Following his second chemotherapy course he underwent a stem cell transplant, and last october doctors performed surgery to remove the tumours from his body.

the surgery was supposed to last seven hours - but he was under the knife for nearly 13 hours after doctors discovered there were more lumps than they thought.

Some tumours were too close to his nervous system or in risky locations, like his lungs, and could not be taken out.

"When they went inside and looked at some tumours they were too close to certain nerves," Jehad said.

"So they had to get some other experts from different fields in the hospital to come in and look at them and make a decision right then and there.

"Plus, I think there were more tumours than they had expected. they didn't see them on the scan."

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Cancer survivor follows his dream of launching a craft beer business

Windows bug-testing software cracks stem cell programs

SOFTWARE used to keep bugs out of Microsoft Windows programs has begun shedding light on one of the big questions in modern science: how stem cells decide what type of tissue to become.

Not only do the results reveal that cellular decision-making is nowhere near as complicated as expected, they also raise hopes that the software could become a key tool in regenerative medicine.

"It is a sign of the convergence between carbon and silicon-based life," says Chris Mason, a regenerative medicine specialist at University College London. "World-class stem cell scientists and a world-class computer company have found common ground. It is work at such interfaces that brings the big breakthroughs."

Stem cells are the putty from which all tissues of the body are made. That means they have the potential to repair damaged tissue and even grow into new organs.

Embryonic stem cells hold particular promise as they can either renew themselves indefinitely or differentiate into any kind of cell in the body a property known as pluripotency.

The process that sets a stem cell on the path to either self-renewal or differentiation was thought to be a highly complex web of genetic and environmental interactions. That web is known as the interactome.

Embryonic stem cells are currently being trialled as a way to restore vision and treat spinal injury. But these trials, and others in the pipeline, are hampered by the fact that no one really knows what determines the fate of any particular stem cell. Today's techniques for making a stem cell differentiate into a certain tissues are hit-and-miss, says Mason.

What's needed is a more deterministic, reliable method, says Sara-Jane Dunn, a computational biologist at Microsoft Research in Cambridge. One approach is to frame the problem in the language of computation. The genetic and environmental cues that determine the cell's fate can be thought of as inputs, with the cell itself as the processor, Dunn says.

Stem cells' capacity to renew themselves is the simplest of the two possible paths out of the pluripotent state. To find the program behind this, Dunn, along with stem cell scientists Graziano Martello at the University of Padua in Italy, and Austin Smith at the University of Cambridge, tried to isolate the genetic and environmental processes at work in mouse embryonic stem cells.

They used a technique pioneered at Smith's lab that uses cultures of various inhibitory proteins to keep embryonic stem cells continually renewing themselves rather than differentiating into other cells. The team immersed the stem cells in four different types of these cultures and analysed which genes they expressed in which environment, and to what extent.

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Windows bug-testing software cracks stem cell programs

Researchers use human stem cells to create light-sensitive retina in a dish

PUBLIC RELEASE DATE:

10-Jun-2014

Contact: Lauren Nelson lnelso35@jhmi.edu 410-955-8725 Johns Hopkins Medicine

Using a type of human stem cell, Johns Hopkins researchers say they have created a three-dimensional complement of human retinal tissue in the laboratory, which notably includes functioning photoreceptor cells capable of responding to light, the first step in the process of converting it into visual images.

"We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light," says study leader M. Valeria Canto-Soler, Ph.D., an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine. She says the work, reported online June 10 in the journal Nature Communications, "advances opportunities for vision-saving research and may ultimately lead to technologies that restore vision in people with retinal diseases."

Like many processes in the body, vision depends on many different types of cells working in concert, in this case to turn light into something that can be recognized by the brain as an image. Canto-Soler cautions that photoreceptors are only part of the story in the complex eye-brain process of vision, and her lab hasn't yet recreated all of the functions of the human eye and its links to the visual cortex of the brain. "Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start," she says.

The achievement emerged from experiments with human induced pluripotent stem cells (iPS) and could, eventually, enable genetically engineered retinal cell transplants that halt or even reverse a patient's march toward blindness, the researchers say.

The iPS cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body. In this case, the Johns Hopkins team turned them into retinal progenitor cells destined to form light-sensitive retinal tissue that lines the back of the eye.

Using a simple, straightforward technique they developed to foster the growth of the retinal progenitors, Canto-Soler and her team saw retinal cells and then tissue grow in their petri dishes, says Xiufeng Zhong, Ph.D., a postdoctoral researcher in Canto-Soler's lab. The growth, she says, corresponded in timing and duration to retinal development in a human fetus in the womb. Moreover, the photoreceptors were mature enough to develop outer segments, a structure essential for photoreceptors to function.

Retinal tissue is complex, comprising seven major cell types, including six kinds of neurons, which are all organized into specific cell layers that absorb and process light, "see," and transmit those visual signals to the brain for interpretation. The lab-grown retinas recreate the three-dimensional architecture of the human retina. "We knew that a 3-D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina," says Canto-Soler, "but when we began this work, we didn't think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do."

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Researchers use human stem cells to create light-sensitive retina in a dish

Dr. Omar Gonzalez presents Best Stem Cell Therapy in Mexico: Integrative Medicine Clinic – Video


Dr. Omar Gonzalez presents Best Stem Cell Therapy in Mexico: Integrative Medicine Clinic
http://www.placidway.com/profile/705/ - Watch this Video as Dr.Omar Gonzalez, MD, specialist in Stem Cell Therapy, Integrative Medicine and Chronic Diseases, presents his new clinic located...

By: placidways

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Dr. Omar Gonzalez presents Best Stem Cell Therapy in Mexico: Integrative Medicine Clinic - Video

Edmond Woman With MS Undergoes Stem Cell Treatment

EDMOND, Oklahoma -

A former Edmond school teacher battling Multiple Sclerosis went to Chicago for a life-saving stem cell transplant. She's back in town now with her results.

Pamela Gooch says she's the first person with Progressive Relapsing MS to have this particular procedure done. And since the transplant, she's never felt better.

"That just terrible tiredness is gone," said Pamela.

Back to her old, playful self, Pamela says her recent stem cell transplant has given her a new life.

"I can take a nap when I tire and I feel rested, however before, I couldn't get out of bed," Pamela said.

For two years since her MS diagnosis, Pamela always felt drained as her immune system was attacking itself. She even chopped off all her hair before chemotherapy beat her to it.

5/3/2014 Related Story: OK Woman Shaves Head To Prepare For MS Treatment

And in a 20 minute operation only offered in Chicago, she got new stem cells placed in her body. It was a success, until she got a letter from her insurance company backing out of covering the $150,000 procedure and instead opting to pay only a 1/10 of it.

"Pay for the rest of our lives for it, this is what we're going to do."

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Edmond Woman With MS Undergoes Stem Cell Treatment

Umbilical cord blood helps to save lives

SOUTH BEND, Ind.--- In the 1970's, researchers discovered that a newborn's umbilical cord blood contained special stem cells that could help fight certain diseases.

More than 30 years later doctors are still experimenting and learning more about the use of cord blood.

Amanda Canale doesn't take time with her daughter and niece for granted.

She's just happy to feel good.

"I've been in the hospital, and I've been sick my whole life," said Amanda.

Amanda was born with a rare blood disorder that required daily shots.

"Basically, I have no white blood cells. I have no immune system at all," said Amanda

At 23 she developed Leukemia and was given two weeks to live.

She desperately needed a Bone Marrow Transplant, but family members weren't matches.

Her doctor suggested an Umbilical Cord Blood Transplant.

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Umbilical cord blood helps to save lives

Stem-cell advances may quell ethics debate

LOUISVILLE, Ky. -- Robert Waddell says he's glad the stem cells that healed him came from "a guy who was 50 years old" and not a human embryo.

As a Catholic, Waddell opposes the destruction of embryos and didn't want to rely on embryonic stem cells to cure his kidney disease. But he avoided this moral dilemma by getting bone marrow stem cells from a friend who donated a kidney as part of a University of Louisville study.

"It has nothing to do with embryonic stem cells," said Waddell, a 47-year-old father of four. "That made it a lot easier."

Recent strides in stem-cell research show adult stem cells to be ever-more-promising, many scientists say, quelling the controversy steeped in faith and science that has long surrounded embryonic stem cells.

In fact, University of Louisville researcher Scott Whittemore said the debate is almost moot.

"Realistically, (many scientists don't use) the types of stem cells that are so problematic anymore," he said, adding that adult stem cells can now be reprogrammed to behave like embryonic stem cells. "The field has moved so fast."

In addition to these genetically reprogrammed adult cells - known as induced pluripotent stem cells or iPS cells - scientists are on the cusp of being able to turn one type of cell into another in the body without using stem cells at all. They shared some of the latest research last week at the annual International Society for Stem Cell Research in Vancouver.

"IPS cells overcame the main ethical issues," namely the use of embryos some Americans consider sacred human life, said Brett Spear, a professor of microbiology, immunology and molecular genetics at the University of Kentucky who uses iPS cells to model liver disease.

But other scientists argue that embryonic stem cell research remains important.

Dr. George Daley, director of the stem cell transplant program at Boston Children's Hospital and past president of the research society, said embryonic cells are a tool in the search for cures.

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Stem-cell advances may quell ethics debate