Tagged: Stem Cell Research Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 2:37 pm on January 15, 2018 Permalink | Reply
    Tags: , , BMPs-bone morphogenetic proteins, Sensory interneurons, Stem Cell Research,   

    From UCLA Newsroom: “UCLA scientists make cells that enable the sense of touch” 


    UCLA Newsroom

    January 11, 2018
    Sarah C.P. Williams

    Researchers are the first to create sensory interneurons from stem cells.

    1
    Human embryonic stem cell-derived neurons (green) showing nuclei in blue. Left: with retinoic acid added. Right: with retinoic acid and BMP4 added, creating proprioceptive sensory interneurons (pink). UCLA Broad Stem Cell Research Center/Stem Cell Reports.

    Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have, for the first time, coaxed human stem cells to become sensory interneurons — the cells that give us our sense of touch. The new protocol could be a step toward stem cell–based therapies to restore sensation in paralyzed people who have lost feeling in parts of their body.

    The study, which was led by Samantha Butler, a UCLA associate professor of neurobiology and member of the Broad Stem Cell Research Center, was published today in the journal Stem Cell Reports.

    Sensory interneurons, a class of neurons in the spinal cord, are responsible for relaying information from throughout the body to the central nervous system, which enables the sense of touch. The lack of a sense of touch greatly affects people who are paralyzed. For example, they often cannot feel the touch of another person, and the inability to feel pain leaves them susceptible to burns from inadvertent contact with a hot surface.

    “The field has for a long time focused on making people walk again,” said Butler, the study’s senior author. “‘Making people feel again doesn’t have quite the same ring. But to walk, you need to be able to feel and to sense your body in space; the two processes really go hand in glove.”

    In a separate study, published in September by the journal eLife, Butler and her colleagues discovered how signals from a family of proteins called bone morphogenetic proteins, or BMPs, influence the development of sensory interneurons in chicken embryos. The Stem Cell Reports research applies those findings to human stem cells in the lab.

    When the researchers added a specific bone morphogenetic protein called BMP4, as well as another signaling molecule called retinoic acid, to human embryonic stem cells, they got a mixture of two types of sensory interneurons. DI1 sensory interneurons give people proprioception — a sense of where their body is in space — and dI3 sensory interneurons enable them to feel a sense of pressure.

    The researchers found the identical mixture of sensory interneurons developed when they added the same signaling molecules to induced pluripotent stem cells, which are produced by reprogramming a patient’s own mature cells such as skin cells. This reprogramming method creates stem cells that can create any cell type while also maintaining the genetic code of the person they originated from. The ability to create sensory interneurons with a patient’s own reprogrammed cells holds significant potential for the creation of a cell-based treatment that restores the sense of touch without immune suppression.

    Butler hopes to be able to create one type of interneuron at a time, which would make it easier to define the separate roles of each cell type and allow scientists to start the process of using these cells in clinical applications for people who are paralyzed. However, her research group has not yet identified how to make stem cells yield entirely dI1 or entirely dI3 cells — perhaps because another signaling pathway is involved, she said.

    The researchers also have yet to determine the specific recipe of growth factors that would coax stem cells to create other types of sensory interneurons.

    The group is currently implanting the new dI1 and dI3 sensory interneurons into the spinal cords of mice to understand whether the cells integrate into the nervous system and become fully functional. This is a critical step toward defining the clinical potential of the cells.

    “This is a long path,” Butler said. “We haven’t solved how to restore touch but we’ve made a major first step by working out some of these protocols to create sensory interneurons.”

    The research was supported by grants from the California Institute for Regenerative Medicine and its Cal State Northridge–UCLA Bridges to Stem Cell Research program, the National Institutes of Health and the UCLA Broad Stem Cell Research Center.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

    Advertisements
     
  • richardmitnick 2:20 pm on November 18, 2017 Permalink | Reply
    Tags: , , , , Stanford University-Engineering, Stem Cell Research   

    From Stanford University – Engineering: “An advance in stem-cell development could help lead to new therapies” 

    Stanford University Name
    Stanford University – Engineering

    November 02, 2017
    Andrew Myers

    1
    Stem cells hold the promise of being able to cure ills ranging from spinal cord injuries to cancers. | Image by: luismmolina/Getty Images

    In many ways, stem cells are the divas of the biological world. On the one hand, these natural shapeshifters can transform themselves into virtually any type of cell in the body. In that regard, they hold the promise of being able to cure ills ranging from spinal cord injuries to cancers.

    On the other hand, said associate professor of materials science and engineering Sarah Heilshorn, stem cells, like divas, are also mercurial and difficult to work with.

    “We just don’t know how to efficiently and effectively grow massive numbers of stem cells and keep them in their regenerative state,” Heilshorn said. “This has prevented us from making more progress in creating therapies.”

    Until now, that is. In a recent paper in Nature Materials, Heilshorn described a solution to the dual challenges of growing and preserving neural stem cells in a state where they are still able to mature into many different cell types. The first challenge is that growing stem cells in quantity requires space. Like traditional farming, it is a two-dimensional affair. If you want more wheat, corn or stem cells, you need more surface area. Culturing stem cells, therefore, requires a lot of relatively expensive laboratory real estate, not to mention the energy and nutrients necessary to pull it all off.

    The second challenge is that once they’ve divided many times in a lab dish, stem cells do not easily remain in the ideal state of readiness to become other types of cells. Researchers refer to this quality as “stemness.” Heilshorn found that for the neural stem cells she was working with, maintaining the cells’ stemness requires the cells to be touching.

    Heilshorn’s team was working with a particular type of stem cell that matures into neurons and other cells of the nervous system. These types of cells, if produced in sufficient quantities, could generate therapies to repair spinal cord injuries, counteract traumatic brain injury or cure some of the most severe degenerative disorders of the nervous system, like Parkinson’s and Huntington’s diseases.

    Seeking stemness

    Heilshorn’s solution involves the use of better materials in which to grow stem cells. Her lab has developed new polymer-based gels that allow the cells to be grown in three dimensions instead of two. This new 3-D process takes up less than 1 percent of the lab space required by current stem cell culturing techniques. And because cells are so tiny, the 3-D gel stack is just a single millimeter tall, roughly the thickness of a dime.

    “For a 3-D culture, we need only a 4-inch-by-4-inch plot of lab space, or about 16 square inches. A 2-D culture requires a plot four feet by four feet, or about 16 square feet,” more than 100-times the space, according to first author Chris Madl, a recent doctoral graduate in bioengineering from Heilshorn’s lab

    In addition to the dramatic savings of lab space, the new process demands fewer nutrients and less energy, as well.

    The gels the team developed allow the stem cells to remodel the long molecules and maintain physical contact with one another to preserve critical communication channels between cells. “The simple act of touching is key to communication between stem cells and to maintaining stemness. If stem cells can’t remodel the gels, they can’t touch one another,” Madl explained.

    “The stem cells don’t exactly die if they can’t touch, but they lose that ability to regenerate that we really need for therapeutic success,” Heilshorn added.

    Striking results

    This need for neural stem cell to remodel their environment differs from what Heilshorn has found in working with other types of stem cells. For those cells, it is the stiffness of the gels – not the ability to remodel – that is the key factor in maintaining stemness. It is as if for these other types of stem cells, gels must mimic the rigidity of the tissue in which the cells will eventually be transplanted. Not so with neural progenitors, said Heilshorn.

    “Neural cell stemness is not sensitive to stiffness and that was a big surprise to us,” she said.

    The result was so striking and unexpected that Heilshorn, at first, didn’t believe her own results. The lab ended up testing three entirely different gels to see if their conclusion held, an unusual supplementary step in this kind of research. With each new material, they saw that those that could be remodeled produced quality stem cells; those that could not be remodeled had a negative effect on stemness.

    Next up on Heilshorn’s research agenda is to create gels that can be injected directly from the lab dish into the body. The possibilities have her feeling optimistic about stem cell therapies again. For a time, she said, it felt as if the field had hit a wall, as initial excitement for regeneration gave way to uninspiring results in the clinic. With her new finding, she said, it feels like new things may be just around the corner.

    “There’s this convergence of biological knowledge and engineering principles in stem cell research that has me hopeful we might finally actually solve some big problems,” she said.

    See the full article here .

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

    Stanford University Seal

     
  • richardmitnick 7:45 pm on July 11, 2017 Permalink | Reply
    Tags: , , Neural Stem Cells Steered by Electric Fields in Rat Brain, Stem Cell Research,   

    From UC Davis: “Neural Stem Cells Steered by Electric Fields in Rat Brain” 

    UC Davis bloc

    UC Davis

    July 11, 2017
    Andy Fell
    ahfell@ucdavis.edu

    Min Zhao
    minzhao@ucdavis.edu

    1
    Transplants of neural stem cells might be used to treat brain injuries, but how to get them to the right location? UC Davis researcher Min Zhao and Junfeng Feng, a neurosurgeon at Ren Ji Hospital, Shanghai, showed that they can steer transplanted stem cells (green, in inset on right) to one part of a rat’s brain using electrical fields. (Image: Junfeng Feng)

    Electric fields can be used to guide neural stem cells transplanted into the brain toward a specific location. The research, published July 11 in the journal Stem Cell Reports, opens possibilities for effectively guiding stem cells to repair brain damage.

    Professor Min Zhao at the University of California, Davis, School of Medicine’s Institute for Regenerative Cures studies how electric fields can guide wound healing. Damaged tissues generate weak electric fields, and Zhao’s research has shown how these electric fields can attract cells into wounds to heal them.

    “One unmet need in regenerative medicine is how to effectively and safely mobilize and guide stem cells to migrate to lesion sites for repair,” Zhao said. “Inefficient migration of those cells to lesions is a significant roadblock to developing effective clinical applications.”

    Junfeng Feng, a neurosurgeon at Ren Ji Hospital, Shanghai Jiao Tong University and Shanghai Institute of Head Trauma, visited Zhao’s lab to study how electric fields might guide stem cells implanted in the brain.

    Natural neural stem cells — cells that can develop into other brain tissues — are found deep in the brain, in the subventricular zone and hippocampus. To repair damage to the outer layers of the brain (the cortex), they have to migrate some distance, especially in the large human brain. Transplanted stem cells might also have to migrate some way to find an area of damage.

    Stem cells move ‘upstream’

    Feng and Zhao developed a model of stem cell transplants in rats. They placed human neural stem cells in the rostral migration stream — a pathway in the rat brain that carries cells toward the olfactory bulb, which governs the animal’s sense of smell. Cells move along this pathway partly carried by the flow of cerebrospinal fluid and partly guided by chemical signals.

    By applying an electric field within the rat’s brain, they found that they could get the transplanted stem cells to swim “upstream” against the fluid flow and natural cues and head for other locations within the brain.

    The transplanted stem cells were still in their new locations weeks or months after treatment.

    “Electrical mobilization and guidance of stem cells in the brain therefore provides a potential approach to facilitate stem cell therapies for brain diseases, stroke and injuries,” Zhao said.

    Additional authors on the paper are: at UC Davis, Lei Zhang, Jing Liu, Bruce Lyeth and Jan Nolta; Ji-Yao Jiang, Ren Ji Hospital, Shanghai Jiao Tong University and Shanghai Institute of Head Trauma; and Michael Russell, Aaken Laboratories, Davis. The work was supported by the California Institute for Regenerative Medicine with additional support from NIH, NSF and Research to Prevent Blindness Inc.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    UC Davis Campus

    The University of California, Davis, is a major public research university located in Davis, California, just west of Sacramento. It encompasses 5,300 acres of land, making it the second largest UC campus in terms of land ownership, after UC Merced.

     
  • richardmitnick 1:28 pm on June 28, 2017 Permalink | Reply
    Tags: , HUJI, Ido Sagi, , Stem Cell Research   

    From HUJI: “First ‘haploid’ human stem cells could change the face of medical research; earn Kaye Innovation Award” 

    Hebrew U of Jerusalem bloc

    The Hebrew University

    1
    Doctoral student and Kaye Innovation Award winner Ido Sagi at the Hebrew University of Jerusalem (Credit: Hebrew University)

    28/06/2017

    Potential for regenerative medicine and cancer research earns doctoral student Ido Sagi a Kaye Innovation Award

    Stem cell research holds huge potential for medicine and human health. In particular, human embryonic stem cells (ESCs), with their ability to turn into any cell in the human body, are essential to the future prevention and treatment of disease.

    One set or two? Diploid versus haploid cells

    Most of the cells in our body are diploid, which means they carry two sets of chromosomes — one from each parent. Until now, scientists have only succeeded in creating haploid embryonic stem cells — which contain a single set of chromosomes — in non-human mammals such as mice, rats and monkeys. However, scientists have long sought to isolate and replicate these haploid ESCs in humans, which would allow them to work with one set of human chromosomes as opposed to a mixture from both parents.

    This milestone was finally reached when Ido Sagi, working as a PhD student at the Hebrew University of Jerusalem’s Azrieli Center for Stem Cells and Genetic Research, led research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans. Unlike in mice, these haploid stem cells were able to differentiate into many other cell types, such as brain, heart and pancreas, while retaining a single set of chromosomes.

    With Prof. Nissim Benvenisty, Director of the Azrieli Center, Sagi showed that this new human stem cell type will play an important role in human genetic and medical research. It will aid our understanding of human development – for example, why we reproduce sexually instead of from a single parent. It will make genetic screening easier and more precise, by allowing the examination of single sets of chromosomes. And it is already enabling the study of resistance to chemotherapy drugs, with implications for cancer therapy.

    Diagnostic kits for personalized medicine

    Based on this research, Yissum, the Technology Transfer arm of the Hebrew University, launched the company New Stem, which is developing a diagnostic kit for predicting resistance to chemotherapy treatments. By amassing a broad library of human pluripotent stem cells with different mutations and genetic makeups, NewStem plans to develop diagnostic kits for personalized medication and future therapeutic and reproductive products.

    2017 Kaye innovation Award

    In recognition of his work, Ido Sagi was awarded the Kaye Innovation Award for 2017.

    The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society.

    Ido Sagi received BSc summa cum laude in Life Sciences from the Hebrew University, and currently pursues a PhD at the laboratory of Prof. Nissim Benvenisty at the university’s Department of Genetics in the Alexander Silberman Institute of Life Sciences. He is a fellow of the Adams Fellowship of the Israel Academy of Sciences and Humanities, and has recently received the Rappaport Prize for Excellence in Biomedical Research. Sagi’s research focuses on studying genetic and epigenetic phenomena in human pluripotent stem cells, and his work has been published in leading scientific journals, including Nature, Nature Genetics and Cell Stem Cell.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Hebrew University of Jerusalem campus

    The Hebrew University of Jerusalem, founded in 1918 and opened officially in 1925, is Israel’s premier university as well as its leading research institution. The Hebrew University is ranked internationally among the 100 leading universities in the world and first among Israeli universities.

    The recognition the Hebrew University has attained confirms its reputation for excellence and its leading role in the scientific community. It stresses excellence and offers a wide array of study opportunities in the humanities, social sciences, exact sciences and medicine. The university encourages multi-disciplinary activities in Israel and overseas and serves as a bridge between academic research and its social and industrial applications.

    The Hebrew University has set as its goals the training of public, scientific, educational and professional leadership; the preservation of and research into Jewish, cultural, spiritual and intellectual traditions; and the expansion of the boundaries of knowledge for the benefit of all humanity.

     
  • richardmitnick 12:13 pm on June 17, 2017 Permalink | Reply
    Tags: , , , , Stem Cell Research   

    From HMS: “Staving Off Stem Cell Cancer Risk” 

    Harvard University

    Harvard University

    Harvard Medical School

    Harvard Medical School

    April 26, 2017 [Never saw this one.]
    HANNAH ROBBINS

    1
    Image: BlackJack3D/Getty Images

    Regenerative medicine using human pluripotent stem cells to grow transplantable tissue outside the body carries the promise to treat a range of intractable disorders, such as diabetes and Parkinson’s disease.

    As stem cell lines grow in a lab dish, however, they often acquire mutations in the TP53 (p53) gene, an important tumor suppressor responsible for controlling cell growth and division, according to new research from a team at Harvard Medical School, the Harvard Stem Cell Institute and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.

    The findings suggest that genetic sequencing technologies should be used to screen stem cell cultures so that those with mutated cells can be excluded from scientific experiments and clinical therapies. If such methods are not employed, the researchers said, it could lead to an elevated cancer risk in patients receiving transplants.

    The paper, published online in the journal Nature on April 26, comes at just the right time, the researchers said, as experimental treatments using human pluripotent stem cells are ramping up across the country.

    “Our results underscore the need for the field of regenerative medicine to proceed with care,” said the study’s co-corresponding author, Kevin Eggan, a principal faculty member at HSCI and director of stem cell biology at the Stanley Center.

    The team said that the new research should not discourage the pursuit of experimental treatments, but instead should be heeded as a call to rigorously screen all cell lines for mutations at various stages of development as well as immediately before transplantation.

    “Fortunately,” said Eggan, this additional series of genetic quality-control checks “can be readily performed with precise, sensitive and increasingly inexpensive sequencing methods.”

    Hidden mutations

    Researchers can use human stem cells to recreate human tissue in the lab. Eggan’s lab in Harvard University’s Department of Stem Cell and Regenerative Biology uses human stem cells to study the mechanisms of brain disorders, including amyotrophic lateral sclerosis, intellectual disability and schizophrenia.

    Eggan has also been working with Steve McCarroll, associate professor of genetics at HMS and director of genetics at the Stanley Center, to study how genes shape the biology of neurons, which can be derived from human stem cells.

    McCarroll’s lab recently discovered a common precancerous condition in which a blood stem cell in the body acquires a so-called pro-growth mutation and then outcompetes a person’s normal stem cells, becoming the dominant generator of that person’s blood cells. People with this condition are 12 times more likely to develop blood cancer later in life.

    The current study’s lead authors, Florian Merkle and Sulagna Ghosh, collaborated with Eggan and McCarroll to test whether laboratory-grown stem cells might be vulnerable to an analogous process.

    “Cells in the lab, like cells in the body, acquire mutations all the time,” said McCarroll, co-corresponding author of the study. “Mutations in most genes have little impact on the larger tissue or cell line. But cells with a pro-growth mutation can outcompete other cells, become very numerous and ‘take over’ a tissue.”

    “We found that this process of clonal selection—the basis of cancer formation in the body—is also routinely happening in laboratories.”

    A p53 problem

    To find acquired mutations, the researchers performed genetic analyses on 140 stem cell lines. Twenty-six lines had been developed for therapeutic purposes using Good Manufacturing Practices, a quality control standard set by regulatory agencies in multiple countries. The remaining 114 were listed on the NIH registry of human pluripotent stem cells.

    “While we expected to find some mutations, we were surprised to find that about 5 percent of the stem cell lines we analyzed had acquired mutations in a tumor-suppressing gene called p53,” said Merkle.

    Nicknamed the “guardian of the genome,” p53 controls cell growth and cell death. People who inherit p53 mutations develop a rare disorder called Li-Fraumeni syndrome, which confers a near 100 percent risk of developing cancer in a wide range of tissue types.

    The specific mutations that the researchers observed are dominant negative mutations, meaning that when present on even one copy of p53, they compromise the function of the normal protein. The same dominant negative mutations are among the most commonly observed mutations in human cancers.

    “They are among the worst p53 mutations to have,” said co-lead author Ghosh.

    The researchers performed a sophisticated set of DNA analyses to rule out the possibility that these mutations had been inherited rather than acquired as the cells grew in the lab.

    Ensuring safety

    In subsequent experiments, the scientists found that p53 mutant cells outperformed and outcompeted nonmutant cells in the lab dish. In other words, a culture with a million healthy cells and one p53 mutant cell, said Eggan, could quickly become a culture of only mutant cells.

    “The spectrum of tissues at risk for transformation when harboring a p53 mutation includes many of those that we would like to target for repair with regenerative medicine using human pluripotent stem cells,” said Eggan.

    Those organs include the pancreas, brain, blood, bone, skin, liver and lungs.

    However, Eggan and McCarroll emphasized that now that this phenomenon has been found, inexpensive gene-sequencing tests will allow researchers to identify and remove from the production line cell cultures with concerning mutations that might prove dangerous after transplantation.

    The researchers point out in their paper that screening approaches already exist to identify these p53 mutations and others that confer cancer risk. Such techniques are being used in cancer diagnostics.

    In fact, an ongoing clinical trial that is transplanting cells derived from induced pluripotent stem cells (iPSCs) is using gene sequencing to ensure the transplanted cell products are free of dangerous mutations.

    This work was supported by the Harvard Stem Cell Institute, the Stanley Center for Psychiatric Research, the Rosetrees Trust, the Azrieli Foundation, the Howard Hughes Medical Institute, the Wellcome Trust, the Medical Research Council, the Academy of Medical Sciences and grants from the National Institutes of Health (HL109525, 5P01GM099117, 5K99NS08371, HG006855, MH105641).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    HMS campus

    Established in 1782, Harvard Medical School began with a handful of students and a faculty of three. The first classes were held in Harvard Hall in Cambridge, long before the school’s iconic quadrangle was built in Boston. With each passing decade, the school’s faculty and trainees amassed knowledge and influence, shaping medicine in the United States and beyond. Some community members—and their accomplishments—have assumed the status of legend. We invite you to access the following resources to explore Harvard Medical School’s rich history.

    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 12:29 pm on May 31, 2017 Permalink | Reply
    Tags: , , Human embryonic stem (ES) cells, , , , Stem Cell Research   

    From Nature: “Trials of embryonic stem cells to launch in China” 

    Nature Mag
    Nature

    31 May 2017
    David Cyranoski

    1
    Former Chinese leader Deng Xiaoping had Parkinson’s disease, one of the first targets of embryonic-stem-cell therapies being tested in China.

    In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject 4 million immature neurons derived from human embryonic stem cells into their brains. Then they will patch the patients up, send them home and wait.

    This will mark the start of the first clinical trial in China using human embryonic stem (ES) cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. In a second trial starting around the same time, a different team in Zhengzhou will use ES cells to target vision loss caused by age-related macular degeneration.

    The experiments will also represent the first clinical trials of ES cells under regulations that China adopted in 2015, in an attempt to ensure the ethical and safe use of stem cells in the clinic. China previously had no clear regulatory framework, and many companies had used that gap as an excuse to market unproven stem-cell treatments.

    “It will be a major new direction for China,” says Pei Xuetao, a stem-cell scientist at the Beijing Institute of Transfusion Medicine who is on the central-government committee that approved the trials. Other researchers who work on Parkinson’s disease, however, worry that the trials might be misguided.

    Both studies will take place at the First Affiliated Hospital of Zhengzhou University in Henan province. In the first, surgeons will inject ES-cell-derived neuronal-precursor cells into the brains of individuals with Parkinson’s disease. The only previous trial using ES cells to treat Parkinson’s began last year in Australia; participants there received stem cells from parthenogenetic embryos — unfertilized eggs that are triggered in the lab to start embryonic development.

    In the other Zhengzhou trial, surgeons will take retinal cells derived from ES cells and transplant them into the eyes of people with age-related macular degeneration. The team will follow a similar procedure to that of previous ES-cell trials carried out by researchers in the United States and South Korea.

    Qi Zhou, a stem-cell specialist at the Chinese Academy of Sciences Institute of Zoology in Beijing, is leading both efforts. For the Parkinson’s trial, his team assessed hundreds of candidates and have so far have picked ten who best match the ES cells in the cell bank, to reduce the risk of the patients’ bodies rejecting the cells.

    The 2015 regulations state that hospitals planning to carry out stem-cell clinical work must use government-certified ES-cell lines and pass hospital-review procedures. Zhou’s team completed four years of work with a monkey model of Parkinson’s, and has met the government requirements, he says.

    Parkinson’s disease is caused by a deficit in dopamine produced by brain cells. Zhou’s team will coax ES cells to develop into precursors to neurons, and will then inject them into the striatum, a central region of the brain implicated in the disease.

    In their unpublished study of 15 monkeys, the researchers did not observe any improvements in movement at first, says Zhou. But at the end of the first year, the team examined the brains of half the monkeys and found that the stem cells had turned into dopamine-releasing cells. He says that they saw 50% improvement in the remaining monkeys over the next several years. “We have all the imaging data, behavioural data and molecular data to support efficacy,” he says. They are preparing a publication, but Zhou says that they wanted to collect a full five years’ worth of animal data.

    Maturity concerns

    Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, who is also planning stem-cell trials for Parkinson’s, is concerned that the Australian and Chinese trials use neural precursors and not ES-cell-derived cells that have fully committed to becoming dopamine-producing cells. Precursor cells can turn into other kinds of neurons, and could accumulate dangerous mutations during their many divisions, says Loring. “Not knowing what the cells will become is troubling.”

    But Zhou and the Australian team defend their choices. Russell Kern, chief scientific officer of the International Stem Cell Corporation in Carlsbad, California, which is providing the cells for and managing the Australian trial, says that in preclinical work, 97% of them became dopamine-releasing cells.

    Lorenz Studer, a stem-cell biologist at the Memorial Sloan Kettering Cancer Center in New York City who has spent years characterizing such neurons ahead of his own planned clinical trials, says that “support is not very strong” for the use of precursor cells. “I am somewhat surprised and concerned, as I have not seen any peer-reviewed preclinical data on this approach,” he says.

    Studer’s and Loring’s teams are part of an international consortium that coordinates stem-cell treatments for Parkinson’s. In the next two years, five groups in the consortium plan to run trials using cells fully committed to becoming dopamine-producing cells.

    Regenerative neurobiologist Malin Parmar, who heads one of the teams at Lund University in Sweden, says that the groups “are all rapidly moving towards clinical trials, and this field will be very exciting in the coming years”.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 11:39 am on May 25, 2017 Permalink | Reply
    Tags: , , , Stem Cell Research, Unlimited supply of healthy blood cells, Weill Cornell   

    From Cornell: “Weill Cornell team creates breakthrough on blood disorders” 

    Cornell Bloc

    Cornell University

    May 18, 2017
    Geri Clark
    cunews@cornell.edu

    Story Contacts
    Cornell Chronicle
    George Lowery
    607-255-2171
    gpl5@cornell.edu

    Media Contact
    Jennifer Gundersen
    646-962-9497
    jeg2034@med.cornell.edu

    1
    This image shows reprogrammed hematopoietic stem cells (green) that are arising from mouse cells. These stem cells are developing close to a group of cells, called the vascular niche cells (gray), which provides them with the nurturing factors necessary for the reprogramming. Dr. Raphael Lis/Provided

    Researchers at Weill Cornell Medicine have discovered an innovative method to make an unlimited supply of healthy blood cells from the readily available cells that line blood vessels. This achievement marks the first time any research group has generated such blood-forming stem cells.

    “This is a game-changing breakthrough that brings us closer not only to treat blood disorders, but also deciphering the complex biology of stem-cell self-renewal machinery,” said senior author Dr. Shahin Rafii, director of the Ansary Stem Cell Institute, chief of the Division of Regenerative Medicine and the Arthur B. Belfer Professor at Weill Cornell Medicine.

    “This is exciting because it provides us with a path toward generating clinically useful quantities of normal stem cells for transplantation that may help us cure patients with genetic and acquired blood diseases,” added co-senior author Dr. Joseph Scandura, associate professor of medicine and scientific director of the Silver Myeloproliferative Neoplasms Center at Weill Cornell Medicine.

    Hematopoietic stem cells (HSCs) are long-lasting cells that mature into white blood cells, red blood cells and platelets. Billions of circulating blood cells do not survive long in the body and must be continuously replenished. When this does not happen, severe blood diseases, such as anemia, bleeding or life-threatening infections, can occur. A special property of HSCs is that they can also “self-renew” to form more HSCs. This property allows just a few thousand HSCs to produce all of the blood cells a person has throughout his or her life.

    Researchers have long hoped to find a way to make the body produce healthy HSCs to cure these diseases. But this has never been accomplished, in part because scientists have been unable to engineer a nurturing environment within which stem cells can convert into new, long-lasting cells – until now.

    In a paper published May 17 in Nature, Rafii and his colleagues demonstrate a way to efficiently convert cells that line all blood vessels, called vascular endothelial cells, into abundant, fully functioning HSCs that can be transplanted to yield a lifetime supply of new, healthy blood cells. The research team also discovered that specialized types of endothelial cells serve as that nurturing environment, known as vascular niche cells, and they choreograph the new converted HSCs’ self-renewal. This finding may solve one of the most long-standing questions in regenerative and reproductive medicine: How do stem cells constantly replenish their supply?

    The research team showed in a 2014 Nature study that converting adult human vascular endothelial cells into hematopoietic cells was feasible. However, the team was unable to prove that they had generated true HSCs because human HSCs’ function and regenerative potential can only be approximated by transplanting the cells into mice, which don’t truly mimic human biology.

    To address this issue, the team applied their conversion approach to mouse blood marrow transplant models that are endowed with normal immune function and where definitive evidence for HSC potential could rigorously tested. The researchers took vascular endothelial cells isolated from readily accessible adult mice organs and instructed them to overproduce certain proteins associated with blood stem-cell function. These reprogrammed cells were grown and multiplied in co-culture with the engineered vascular niche. The reprogrammed HSCs were then transplanted as single cells with their progenies into mice that had been irradiated to destroy all of their blood-forming and immune systems, and then monitored to see whether or not they would self-renew and produce healthy blood cells.

    2
    Study co-authors, from left: Dr. Joseph Scandura, Dr. Raphael Lis, Dr. Jason Butler, Michael Poulos, Balvir Kunar Jr., Chaitanya R. Badwe, Koji Shido, Dr. Zev Rozenwaks, Jose-Gabriel Barcia-Duran, Dr. Shahin Rafii and Dr. Jenny Xiang. Not pictured: Charles Karrasch, David Redmond, Dr. Will Schachterle, Michael Ginsberg, Dr. Arash Rafii and Dr. Olivier Elemento. Michael Gutkin’Provided

    The conversion procedure yielded a plethora of transplantable HSCs that regenerated the entire blood system in mice for the duration of their life spans, a phenomenon known as engraftment. “We developed a fully functioning and long-lasting blood system,” said lead author Raphael Lis, an instructor in medicine and reproductive medicine at Weill Cornell Medicine. In addition, the HSC-engrafted mice developed all of the working components of the immune systems. “This is clinically important because the reprogrammed cells could be transplanted to allow patients to fight infections after marrow transplants,” Lis said. The mice in the study went on to live normal-length lives and die natural deaths, with no sign of leukemia or any other blood disorders.

    In collaboration with Olivier Elemento, associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine, and Dr. Jenny Xiang, director of Genomics Services, Rafii and his team also showed the reprogrammed HSCs and their differentiated progenies – including white and red bloods cells, as well as the immune cells – were endowed with the same genetic attributes as that of normal adult stem cells. These findings suggest the reprogramming process results in the generation of true HSCs that have genetic signatures that are very similar to normal adult HSCs.

    The Weill Cornell Medicine team is the first to achieve cellular reprogramming to create engraftable and authentic HSCs, which have been considered the holy grail of stem cell research. “We think the difference is the vascular niche,” said contributing author Jason Butler, assistant professor of regenerative medicine at Weill Cornell Medicine. “Growing stem cells in the vascular niche puts them back into context, where they come from and multiply. We think this is why we were able to get stem cells capable of self-renewing.”

    If this method can be scaled up and applied to humans, it could have wide-ranging clinical implications. “It might allow us to provide healthy stem cells to patients who need bone marrow donors but have no genetic match,” Scandura said. “It could lead to new ways to cure leukemia and myeloproliferative neoplasms, and may help us correct genetic defects that cause blood diseases like sickle-cell anemia.”

    “More importantly, our vascular niche-stem-cell expansion model may be employed to clone the key unknown growth factors produced by this niche that are essential for self-perpetuation of stem cells,” Rafii said. “Identification of those factors could be important for unraveling the secrets of stem cells’ longevity and translating the potential of stem cell therapy to the clinical setting.”

    Additional study co-authors include Charles Karrasch, Michael Poulos, Balvir Kunar, David Redmond, Jose-Gabriel Barcia-Duran, Chaitanya Badwe and Koji Shido of Weill Cornell Medicine; Will Schachterle, formerly of Weill Cornell Medicine; Dr. Arash Rafii of Weill Cornell Medicine-Qatar; Dr. Michael Ginsberg of Angiocrine Bioscience; and Dr. Nancy Speck of the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania.

    Various study authors have relationships with Angiocrine Bioscience that are independent of Weill Cornell Medicine.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

     
  • richardmitnick 12:55 pm on May 17, 2017 Permalink | Reply
    Tags: , Dr Yu Suk Choi, , Stem Cell Research,   

    From UWA: “Researchers uncover new way of growing stem cells” 

    UWA

    University of Western Australia

    16 May 2017
    David Stacey
    UWA Media and Public Relations Manager
    (+61 8) 6488 3229
    (+61 4) 32 637 716

    1
    Dr Yu Suk Choi

    Research led by The University of Western Australia has discovered a new, simple and less expensive way of growing human stem cells.

    Using hydrogel, a gel with a gradient that can be used to mimic the stiffness of human body tissues, the researchers were able to generate positive outcomes for the growth of stem cells.

    Dr Yu Suk Choi from UWA’s School of Human Sciences at The University of Western Australia led the international collaboration which also included researchers from the University of California, San Diego (USA) and Max Planck Institute for Medical Research (Germany).

    “Stem cells work by using the ‘stiffness’ of surrounding tissue as a gauge to identify the way they need to behave in a particular environment in the human body,” Dr Choi said.

    “By using hydrogel to mimic the stiffness of tissue, we found we could ‘trick’ the stem cells into behaving in particular ways to help them grow and encourage the cells to behave in positive, regenerative ways.

    “Hydrogel is simple and inexpensive to produce and could have a wide range of applications in biology labs that don’t always have the infrastructure available to use other methods to mimic the stiffness of tissue to aid stem cell growth.”

    Dr Choi said the research may have important uses in combating serious illnesses affecting the human population.

    “Many degenerative diseases result in changes to tissue stiffness which alters the behavior of cells,” he said.

    “But by controlling tissue stiffness we can revert cell behavior back to normal, and change their behavior at the disease site into more regenerative behaviour. This will help us us to treat diseases such as cancer that are currently very difficult to treat.”

    The next step for the researchers will be to use hydrogel with patient originated cells to further understand the effect of tissue stiffness on cell behaviour.

    The research, published in the PNAS journal, has been made possible through funding from the National Health and Medical Research Council (NHMRC) and Heart Research Australia.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    uwa-campus

    The University of Western Australia (UWA) is a research-intensive university in Perth, Australia that was established by an act of the Western Australian Parliament in February 1911, and began teaching students for the first time in 1913. It is the oldest university in the state of Western Australia. It is colloquially known as a “sandstone university”. It is also a member of the Group of Eight.

    UWA was established under and is governed by the University of Western Australia Act 1911.[2] The Act provides for control and management by the university’s Senate, and gives it the authority, amongst other things, to make statutes, regulations and by-laws, details of which are contained in the university Calendar.[3]

    UWA is highly ranked internationally in various publications: the 2015 QS World University Rankings[4] placed UWA at 98th internationally, and in August 2016 the Academic Ranking of World Universities from Shanghai Jiao Tong University placed the university at 96th in the world.[5] To date, the university has produced 100 Rhodes Scholars;[6] one Nobel Prize laureate[7] and one Australian Prime Minister.[8]

    In 2010 UWA joined the Matariki Network of Universities as the youngest member, the only one established during the 20th century.

     
  • richardmitnick 1:25 pm on February 8, 2017 Permalink | Reply
    Tags: Pluripotent stem cells, Stem Cell Research, , UCLA researchers turn stem cells into somites the precursors to skeletal muscle cartilage and bone   

    From UCLA: “UCLA researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone” 

    UCLA bloc

    UCLA

    February 07, 2017
    Sarah C.P. Williams

    1
    The new protocol turned 90 percent of human pluripotent stem cells into somite cells in just four days; those somite cells then generated (left to right) cartilage, bone and muscle cells. UCLA Broad Stem Cell Research Center/Cell Reports

    FINDINGS

    Adding just the right mixture of signaling molecules — proteins involved in development — to human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage in developing embryos. The somites-in-a-dish then have the potential to generate these cell types in the lab, according to new research led by senior author April Pyle at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

    BACKGROUND

    Pluripotent stem cells, by definition, can become any type of cell in the body, but researchers have struggled to guide them to produce certain tissues, including muscle. In developing human embryos, muscle cells — as well as the bone and cartilage of vertebrae and ribs, among other cell types — arise from small clusters of cells called somites.

    Researchers have studied how somites develop in animals and identified the molecules that seem to be an important part of that process in animals. But when scientists have tried to use those molecules to coax human stem cells to generate somites, the protocols have been inefficient.

    METHOD

    The scientists isolated the minuscule developing human somites and measured expression levels of different genes both before and after the somites were fully formed. For each gene that changed levels during the process, the researchers tested whether adding molecules to boost or suppress the function of that gene in human pluripotent stem cells helped push the cells to become somite-like. They found that the optimal mixture of molecules in humans was different than what had been tried in animals. Using the new combination, they could turn 90 percent of human stem cells into somite cells in just four days.

    The scientists followed the cells over the next four weeks and determined that they were indeed able to generate cells including skeletal muscle, bone and cartilage that normally develop from somites.

    IMPACT

    The new protocol to create somite-like cells from human pluripotent stem cells opens the door to researchers who want to make muscle, bone and cartilage cells in the lab. Pyle’s group plans to study how to use muscle cells generated from the new somites to treat Duchenne muscular dystrophy, a severe form of muscle degeneration that currently does not have a cure.

    AUTHORS

    Pyle is a UCLA associate professor of microbiology, immunology and molecular genetics. The first author of the study is Haibin Xi; co-authors are Wakana Fujiwara, Karen Gonzalez and Majib Jan of UCLA; Katja Schenke-Layland and Simone Liebscher of Germany’s Eberhard Karls University Tübingen; and Ben Van Handel of CarthroniX Inc., a California-based biopharmaceutical company.

    JOURNAL

    The study was published in the journal Cell Reports.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

     
  • richardmitnick 1:33 pm on December 8, 2016 Permalink | Reply
    Tags: , , , Stem Cell Research   

    From Harvard: “Colorful clones track stem cells” 

    Harvard University

    Harvard University

    November 23, 2016 {Just found this in social media.]
    Hannah Robbins, HSCI Communications

    1

    Harvard Stem Cell Institute (HSCI) researchers have used a colorful cell-labeling technique to track the development of the blood system and trace the lineage of adult blood cells traveling through the vast networks of veins, arteries, and capillaries back to their parent stem cells in the marrow.

    Developed at Harvard’s Center for Brain Science, the technique involves coding multiple colors of fluorescent protein into a cell’s DNA. As genes recombine inside the cell, the cell elaborates a color unique to its genetic code. For blood stem cells, that color becomes a genetic signature passed down to daughter cells; purple stem cells, for example, will only make purple blood cells.

    Two independent research teams, one led by David Scadden, HSCI co-director and Gerald and Darlene Jordan Professor of Medicine at Harvard University, and the other by his colleague Leonard Zon, HSCI Executive Committee member and director of the Stem Cell Program at Boston Children’s Hospital, adapted the color-based labeling to the blood system to better understand how blood stem cells behave.

    In a study recently published in Cell, a research team led by Scadden found that in mice individual blood stem cells had a specific and restricted blood production repertoire.

    “We used to think of stem cells as the mother cell that gives rise to all these other cells in the system on an as-needed basis,” said Vionnie Yu, first author of the study and, at the time of the research, a postdoctoral fellow in Scadden’s lab. But their results suggest that stem cells have a scripted set of responses and cannot make just any blood cell type.

    When transplanted into a new environment, each cell not only consistently made the same mature blood cell types but also the same number of those cells. Additionally, clones responded similarly to inflammatory and chemotoxic stress, suggesting the cells had a hardwired memory dictating their behavior. They found that this memory was written into the stem cell epigenome.

    Blood stem cells, said Scadden, may be more like chess pieces with a fixed way they can behave within the system.

    “When you are young and have a full chess set you can mount a vigorous and multilayered defense to an attack on your system,” Scadden said, “but if you lose chess pieces with age or you don’t receive a full suite of players during a bone marrow transplant, the pieces you have left could determine your ability to protect yourself.”

    In addition to looking at blood stem cells in adult mice, color tagging also allows researchers to explore the blood system as a zebrafish embryo develops.

    “We’ve been working with David Scadden for years as part of the HSCI. Initially, we presented our work at a joint lab meeting and realized we could study stem cell clones with this multicolor system,” said Zon, who is also a professor in Harvard’s Stem Cell and Regenerative Biology department. “We shared ideas and results, and even wrote a grant together on the topic. It is wonderful that studying clonal dynamics in two different animals could provide such complementary information.”

    In a study published Monday in Nature Cell Biology, the researcher team led by Zon used the color-tagging system to find the origin and number of stem cells that contribute to lifelong blood production.

    About 24 to 30 hours after fertilization, dozens of stem cells budded off from the dorsal side of the aorta. Only 20 made it to a secondary site before heading to the kidney marrow, the zebrafish equivalent to human and mouse bone marrow.

    After transplanting the multicolored marrow into fish that had received sublethal doses of radiation, the researchers found that some blood stem cell lineages supplied a greater proportion of blood than they had before and that certain lineages could survive harsher conditions than others.

    Knowing which cells are responsible for blood production could have implications for understanding the development of blood cancers, explained Jonathan Henninger, a graduate student in Zon’s lab at Boston Children’s Hospital and first author in the study.

    For example, one cell could develop a mutation that gives it a competitive edge, allowing it to take over the blood system.

    “If that cell starts behaving badly, it could lead to blood disorders, such as myeloid dysplasia and leukemia,” Henninger said.

    Researchers know these disorders come from a single stem cell or a downstream progenitor cell, said Henninger, but right now they are looking at populations of stem cells in bulk. “To be able to identify that single cell that went awry could help us better understand these diseases.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
%d bloggers like this: