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Stem Cells Driving Alzheimer's Research

By raymumme

By Marcus Johnson

Stem cell researchers from Harvard have been able to turn patients skin cells into neurons that can be affected by early-onset Alzheimers. Experts believe that this will make it easier to gather the results of cells affected by the disease. It is also believed that the research will make the development of new treatments a faster process.

The research was published in the Human Molecular Genetics journal and headed by Tracy Young-Pearse. The data showed that peopl suffering from Alzheimers had cell mutations t similar to mutations occurring in mice. We see this mild increase in A42 in cells from patients with Alzheimer's disease, which seems to be enough to trigger disease processes, said Young-Pearse. We also see increases of a smaller species of amyloid-beta called A38, which was unexpected as it should not be very aggregation prone. We don't fully understand what it means, but it may combine with other forms of amyloid-beta to stimulate plaque formation.

The researchers hope that their work can lead to new drugs that are more effective against the disease. Alzheimers drugs have had a high rate of failure during clinical trials because much of the drug development was based on non-human models. Young-Pearse hopes that their research can make it easier to treat the disease and develop new drugs. Because of the Harvard Stem Cell Institute, we were able to work with other researchers to make patient cells into any type of neuron," said Young-Pearse. "The environment provides a really nice system for testing many kinds of hypotheses.

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What's Next for Stem Cells and Regenerative Medicine?

By raymumme

See Inside Mar 19, 2013 |By Christine Gorman

Richard Clark, NIH

Researchers are now experimenting with stem cellsprogenitor cells that can develop into many different types of tissueto coax the bodies of a few individuals to heal themselves. Some of the most advanced clinical trials so far involve treating congestive heart disease and regrowing muscles in soldiers who were wounded in an explosion. But new developments are happening so quickly that investigators have come up with a new nameregenerative medicineto describe the emerging field.

Many of the stem cells being studied are referred to as pluripotent, meaning they can give rise to any of the cell types in the body but they cannot give rise on their own to an entirely new body. (Only the earliest embryonic cells, which occur just after fertilization, can give rise to a whole other organism by themselves.) Other stem cells, such as the ones found in the adult body, are multipotent, meaning they can develop into a limited number of different tissue types.

One of the most common stem cell treatments being studied is a procedure that extracts a few stem cells from a person's body and grows them in large quantities in the laboratorywhat scientists refer to as expanding the number of stem cells. Once a sufficient number have been produced in this manner, the investigators inject them back into the patient.

The bone marrow is a rich source of adult stem cells, containing both the hematopoietic stem cells that give rise to the various types of blood and the so-called mesenchymal cells, which can develop into bone, cartilage and fat. Mesenchymal cells are found in the bone marrow and various other places in the body, although whether all mesenchymal stem cells are truly interchangeable irrespective of origin is unclear.

Scientific American spoke with Mahendra Rao, director of the Center for Regenerative Medicine at the National Institutes of Health in Bethesda, Md., to get a sense of the sorts of new developments that might occur in regenerative medicine in the next five years or so.

[An edited transcript of the interview follows.]

Why is there so much excitement about regenerative medicine? You could say that medicine up until now has been all about replacements. If your heart valve isn't working, you replace it with another valve, say from a pig. With regenerative medicine, you're treating the cause and using your own cells to perform the replacement. The hope is that by regenerating the tissue, you're causing the repairs to grow so that it's like normal.

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21.Spinal Cord Injury(T5-6) Treated by Stem Cell Therapy(Before) – Video

By raymumme


21.Spinal Cord Injury(T5-6) Treated by Stem Cell Therapy(Before)
Patient with T5-6 spinal cord injury: condition before treatment Before treatment, sensation remains only above the waist. Sweating remains only in the upper...

By: Cells Center China

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Horses set to gain health benefits from stem cell advance

By raymumme

PUBLIC RELEASE DATE:

4-Mar-2014

Contact: Jen Middleton jen.middleton@ed.ac.uk 44-131-650-6514 University of Edinburgh

Horses suffering from neurological conditions similar to those that affect humans could be helped by a breakthrough from stem cell scientists.

Researchers who are the first to create working nerve cells from horse stem cells say the advance may pave the way for cell therapies that target conditions similar to motor neurone disease.

The research could also benefit horses affected by grass sickness, a neurological condition that affects around 600 horses a year in the UK.

Little is known about the disease, which causes nerve damage throughout the body. It is untreatable and animals with the most severe form usually die or have to be put down.

The advance by the University of Edinburgh's Roslin Institute will provide a powerful tool for those studying horse diseases. It will also help scientists to test new drugs and treatments.

The researchers took skin cells from a young horse and turned them into stem cells using a technique that was originally developed for human cells. The reprogrammed cells are pluripotent, which means they can be induced to become any type of cell in the body.

The team used them to create nerve cells in the laboratory and tested whether they were functional by showing that they could transmit nerve signals in a test tube.

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Stem Cell Therapy | Stem cells from osteoarthritis patients as good as controls? – Video

By raymumme


Stem Cell Therapy | Stem cells from osteoarthritis patients as good as controls?
http://wwwarthritistreatmentcenter.com Stem cells from patients with osteoarthritis are as good as normal controls Alwin Scharstuhl and colleagues, in an art...

By: Nathan Wei

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Annie – Before Stem Cell – Video

By raymumme


Annie - Before Stem Cell
Here are some REAL results from stem cell therapy. This is Annie before her stem cell therapy treatment.

By: Stacey Ragsdale

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New neurons generated in brains, spinal cords of living adult mammals

By raymumme

UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the body's own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer's disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UT Southwestern's Department of Molecular Biology first successfully turned astrocytes -- the most common non-neuronal brain cells -- into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

"Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons," said Dr. Chun-Li Zhang, assistant professor of molecular biology at UT Southwestern and senior author of both studies.

"Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration," Dr. Zhang explained. "Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming."

The scientists' two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

The current study reports neurogenesis (neuron creation) occurred in the spinal cords of both adult and aged (over one-year old) mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation. Neuroblasts took four weeks to form and eight weeks to mature into neurons, slower than neurogenesis reported in lab dish experiments, so researchers plan to conduct experiments to determine if the slower pace helps the newly generated neurons properly integrate into their environment.

In the spinal cord study, SOX2-induced mature neurons created from reprogramming of astrocytes persisted for 210 days after the start of the experiment, the longest time the researchers examined, he added.

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RoosterBio Inc, a Frederick Maryland Biotech Startup, Achieves Rapid Traction with Product Launch and Fundraising …

By raymumme

Frederick, MD (PRWEB) February 25, 2014

RoosterBio Inc is a new biotech start-up supplying human bone marrow-derived Mesenchymal Stem Cells (hBM-MSC) for tissue engineering research and stem cell-based product development into the high growth Synthetic Biology and Regenerative Medicine fields. RoosterBio, Inc. initiated laboratory operations in October, 2013, and has achieved the critical milestone of first product shipment to paying customers in just four short months. In addition to the early validation of their business model and rapidly generating revenue, Roosterbio has raised over 250K in seed investment and are actively seeking funds via AngelList (https://angel.co/roosterbio).

RoosterBio credits their quick-to-market accomplishments to hyper-efficient operations and the passion that the RoosterBio team shares in their desire to assist tissue engineers and cell therapists to accelerate life-saving technologies into the clinic. Our laser focus coupled with operational excellence has enabled us to reach these milestones; we will delight our customers with our product offering, says Chief Operating Officer, Dr. Uplaksh Kumar. The RoosterBio teams extensive experience sourcing raw materials, manufacturing stem cell products, and controlling for high quality with best-in-class characterization techniques has allowed them to successfully launch their flagship hBM-MSC product quickly and efficiently.

Dr. Jon Rowley, RoosterBios Chief Executive said I cant express how proud I am of our small, highly dedicated team that worked tirelessly to get our first products designed, manufactured, quality tested, released, and just as importantly sold and shipped to our first paying customers. This was truly a team effort that couldnt have been done without each and every person at RoosterBio.

Having spent years as cell and tissue technologists, the RoosterBio team has an intimate understanding of the pain points surrounding the generation of large numbers of robust, reproducible, standardized cells for research and product development purposes. RoosterBio products are designed to solve this problem and they believe that high volume and affordable cellular raw materials will kick-start the cell-based medical product revolution.

Dr. Sarah Griffiths, a Researcher at Georgia Tech in Atlanta, believes that RoosterBios MSCs will do exactly that, and was anxiously awaiting receipt of the product. "We are excited to receive the first shipment of RoosterBios product. The potential to generate large stocks of MSCs in a short period of time will be a tremendous advantage to the progress of our research."

Researchers in the fields of Synthetic Biology and Regenerative Medicine, such as Dr. Griffiths, will use RoosterBios MSCs to develop new medical therapies to provide treatments for degenerative diseases such as Parkinsons and Alzheimers diseases, or to repair or replace tissue after a catastrophic injury such as traumatic bone and cartilage injury, spinal cord damage, heart attack, or significant burns.

RoosterBios current focus is to supply high volume research-grade cells manufactured with processes consistent with current Good Manufacturing Practices (cGMP). They are rapidly approaching their next milestones by laying the groundwork for initiating production of clinical-grade cells to be used in translational R&D and clinical studies.

About RoosterBio RoosterBio is focused on building a robust and sustainable Regenerative Medicine industry. Our products are affordable and standardized primary cells and media, manufactured and delivered with highest quality and in formats that simplify product development efforts. RoosterBio products are made with care in Frederick, MD, and will accelerate the translation of cell therapy and tissue engineering technologies into the clinic.

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Hero stem-cell donor saves brave leukaemia patient Margot Martini

By raymumme

21 Feb 2014 20:33

Staffordshire toddler has life-saving bone marrow transplant after match is finally found

Parents of a brave toddler battling leukaemia hailed a stem-cell donor their hero as their daughter received a life-saving bone marrow transplant.

Vicky and Yaser Martini, from Essington, Staffordshire, launched a huge internet campaign to find a match for 18-month-old Margot after she was diagnosed with two types of the cancer last October.

An estimated 40,000 people have requested donor packs from charity Delete Blood Cancer since the appeal, which has been backed by celebrities Stephen Fry, Gary Barlow and former Wolves hero Steve Bull.

Margot underwent a two-hour bone marrow transplant at Great Ormond Street Hospital in London on Friday after a stem cell donor match, said to be from outside the UK, was confirmed earlier this month.

The toddler napped contentedly in her pram as the stem cells were administered via a Hickman line in her chest said dad Yaser.

This young chap has done this selfless and benevolent thing. Frankly, he is my hero, he added.

I am watching it as it happens. It is quite something.

Margot Martini, with her brothers Rufus and Oscar, her dad Yaser and mum Vicky

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Family of wounded teen marathon victim starts fund

By raymumme

AP/February 20, 2014

BOSTON (AP) The family of a teenager who almost lost a leg in the Boston Marathon bombings has started a fund to explore limb regeneration and the use of stem cells to regrow bones and skin.

Gillian Renys parents started the fund with an undisclosed sum and have formed a team for this years marathon to raise more. The goal is $3 million to fund research intended to help others at risk of amputation.

Reny, as well her parents Audrey Epstein Reny and Steven Reny, havent spoken publicly about their ordeal, but are coming forward now in interviews with The Boston Globe and WCVB-TV to talk about the Gillian Reny Stepping Strong Fund.

Both of Renys legs were injured in the April blast, and doctors were not sure they could save her mangled lower right leg.

I knew from seeing the destruction of my legs that something very serious had happened, Reny said.

Reny was standing near the finish line with her parents to watch her sister complete the race when twin bombs detonated, killing three people and injuring more than 260 others.

Reny, now a 19-year-old freshman at the University of Pennsylvania, is still rehabilitating but is able to walk on her own after undergoing several surgeries.

Initially, doctors did not know if Renys leg could be saved, said plastic surgeon Dr. Eric Halvorson.

But Halvorson found that a vital nerve was undamaged, and tests showed that major blood vessels were largely intact. Reny spent several weeks at Brigham & Womens Hospital and within two months recovered enough to attend her graduation from Buckingham Brown & Nichols School on crutches.

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stem cell therapy treatment for right brachial plexus by dr alok sharma, mumbai, india – Video

By raymumme


stem cell therapy treatment for right brachial plexus by dr alok sharma, mumbai, india
improvement seen in just 5 days after stem cell therapy treatment for right brachial plexus by dr alok sharma, mumbai, india. Stem Cell Therapy done date 21/...

By: Neurogen Brain and Spine Institute

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What is Stem Cell Therapy? – Video

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What is Stem Cell Therapy?
According to J. Peter Rubin, MD, Chair of the University of Pittsburgh #39;s Department of Plastic Surgery, stem cells are small cells that live within the tissu...

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Cancer Researchers Discover Pre-Leukemic Stem Cell at Root of AML, Relapse

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Newswise (TORONTO, Canada Feb. 12, 2014) Cancer researchers led by stem cell scientist Dr. John Dick have discovered a pre-leukemic stem cell that may be the first step in initiating disease and also the culprit that evades therapy and triggers relapse in patients with acute myeloid leukemia (AML).

The research, published online today in Nature (http://dx.doi.org/10.1038/nature13038) is a significant leap in understanding the steps that a normal cell has to go through as it turns into AML, says Dr. Dick, and sets the stage to advance personalized cancer medicine by potentially identifying individuals who might benefit from targeting the pre-leukemic stem cell. AML is an aggressive blood cancer that the new research shows starts in stem cells in the bone marrow. Dr. Dick, a Senior Scientist at Princess Margaret Cancer Centre, University Health Network (UHN), and Professor in the Department of Molecular Genetics, University of Toronto, pioneered the cancer stem cell field by first identifying leukemia stem cells (1994) and colon cancer stem cells (2007).

"Our discovery lays the groundwork to detect and target the pre-leukemic stem cell and thereby potentially stop the disease at a very early stage when it may be more amenable to treatment," says Dr. Dick, who holds a Canada Research Chair in Stem Cell Biology and is also Director of the Cancer Stem Cell Program at the Ontario Institute for Cancer Research (OICR).

VIDEO: Dr. Dick talks about the research at: http://ow.ly/tyLY8.

"Now we have a potential tool for earlier diagnosis that may allow early intervention before the development of full AML. We can also monitor remission and initiate therapy to target the pre-leukemic stem cell to prevent relapse," he says.

The findings show that in about 25% of AML patients, a mutation in the gene DNMT3a causes pre-leukemic stem cells to develop that function like normal blood stem cells but grow abnormally. These cells survive chemotherapy and can be found in the bone marrow at remission, forming a reservoir of cells that may eventually acquire additional mutations, leading to relapse.

The discovery of pre-leukemic stem cells came out of a large Leukemia Disease Team that Dr. Dick assembled and included oncologists who collected samples for the Princess Margaret Cancer Centre Biobank and genome scientists at the OICR who developed sophisticated targeted sequencing methodology. With this team, it was possible to carry out genomic analysis of more than 100 leukemia genes on many patient samples. The findings also capitalized on data from more than six years of experiments in Dr. Dick's lab involving growing human AML in special mice that do not reject human cells.

"By peering into the black box of how cancer develops during the months and years prior to when it is first diagnosed, we have demonstrated a unique finding. People tend to think relapse after remission means chemotherapy didn't kill all the cancer cells. Our study suggests that in some cases the chemotherapy does, in fact, eradicate AML; what it does not touch are the pre-leukemic stem cells that can trigger another round of AML development and ultimately disease relapse," says Dr. Dick, who anticipates the findings will spawn accelerated drug development to specifically target DNMT3a.

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Wayland Baptist hosting bone marrow drive

By raymumme

Provided by: Wayland Baptist University

PLAINVIEW In honor of Lana Watson, Wayland Baptist University is hosting a bone marrow drive on Monday from 4 to 6 p.m. in Pete's Place, the student lounge in the basement of the McClung University Center, in conjunction with Covenant Health Plainview.

Other screening locations are the hospital lab at 2601 Dimmitt Road from 7 to 9 a.m., the South Plains College nursing lab at 1920 W. 24 from 10 a.m. to 12 p.m., and the First Baptist Church parlor at 205 W. 8th from 1 to 3 p.m.

Lana is the wife of Rodney Watson, Director of the Llano Estacado Museum and a deacon at First Baptist Church. Lana is currently in Dallas undergoing a transplant procedure of her own stem cells and waiting while the search for a bone marrow donor continues.

According to Laurie Hall, Coordinator of Health Services at Wayland, donors should be between the ages of 18-44. People over the age of 44 can be screened, but there is a $100 registration fee. Contact Be the Match at http://www.bethematch.orgfor more information.

No needles are involved in the screening process as donor information is collected through a mouth swab and registration process.

Through a similar drive last year, former Wayland student Scott Langford was identified as a match for a transplant patient. Langford donated his bone marrow to save a life.

Everyone interested in donating bone marrow is encouraged to undergo the screening process.

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The Stem Cell Experts – Video

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The Stem Cell Experts
The McGowan Institute for Regenerative Medicine is a program of the University of Pittsburgh and UPMC. The Institute specializes in discovering the potential...

By: Fernanda Torres

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Stem cells cultivated without using human or animal cells

By raymumme

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Previously, stem cells have been cultivated using animal proteins or by growing them from other human cells. Both methods come with associated problems. But, according to a study published in the journal Applied Materials & Interfaces, researchers have now identified a new method for cultivating stem cells.

Stem cells are a kind of cell that are able to divide or self-renew indefinitely. This allows the stem cell to generate into a range of different cell types for the organ that they originate from, or they may even be able to regenerate the whole organ.

Because of this, scientists are interested in using stem cells in a range of medical treatments, to replenish damaged tissue in the brain or skin, or as a treatment for diseases of the blood.

In adults, these stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin and liver. Adult stem cells only become "activated" and start dividing and generating new cells when their host tissue becomes damaged by disease or injury.

A more potent kind of stem cell is found in human embryos - this type has the unique ability to grow into any kind of cell in the human body. But using these cells in scientific research is controversial - and illegal in some countries - as harvesting them requires the destruction of a fertilized human egg (a "blastocyst") that has not had the chance to develop into a baby.

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Gene therapy may be possible cure for Hurler syndrome: Mouse Study

By raymumme

Researchers used blood platelets and bone marrow cells to deliver potentially curative gene therapy to mouse models of the human genetic disorder Hurler syndrome -- an often fatal condition that causes organ damage and other medical complications.

Scientists from Cincinnati Children's Hospital Medical Center and the National Institute of Neurological Disorders and Stroke (NINDS) report their unique strategy for treating the disease the week of Feb. 3-7 in Proceedings of the National Academy of Sciences (PNAS).

Researchers were able to genetically insert into the cells a gene that produces a critical lysosomal enzyme (called IDUA) and then inject the engineered cells into mice to treat the disorder. Follow up tests showed the treatment resulted in a complete metabolic correction of the disease, according to the authors.

"Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes," said Dao Pan, PhD, corresponding author and researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed."

The mice tested in the study modeled human Hurler syndrome, a subset of disease known as mucopolysaccharidosis type I (MPS I), one of the most common types of lysosomal storage diseases. MPS I is a lysosomal storage disease in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).

IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints, according to the National Library of Medicine/National Institutes of Health. Without IDUA, sugar molecules build up and cause organ damage. Depending on severity, the syndrome can also cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.

Enzyme replacement therapy can be used to treat the disease, but it is only temporary and not curative. Bone marrow transplant using hematopoietic stem cells also has been tested on some patients with mixed results. The transplant procedure can carry severe risks and does not always work.

Pan and her colleagues -- including Roscoe O. Brady, MD, a researcher at NINDS -- report that using platelets and megakaryocytes for gene therapy is effective and could reduce the risk of activating cancer-causing oncogenes in hematopoietic stem cells.

The authors said tests showed that human megakaryocytic cells were capable of overexpressing IDUA, revealing their capacity for potential therapeutic benefit. While engineering megakaryocytes and platelets for infusion into their mouse models of Hurler, the scientists report they were able to release IDUA directly into amply sized extracellular spaces or inside micro-particles as the cells matured or activated. The cells were able to produce and package large amounts of functional IDUA and retained the capacity to cross-correct patient cells.

After infusing mouse models of Hurler with the genetically modified cells, researchers said this led to long-term normalization of IDUA levels in the animal's blood with versatile delivery routes and on-target preferential distribution to the liver and spleen. The treatment led to a complete metabolic correction of MPS I in most peripheral organs of the mice.

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Scientists discover how to change skin cells to stem cells …

By raymumme

There are exciting developments in the field of stem cell research which could make the whole thing cheaper, easier, and much quicker. According to a Jan. 29 report on BBC News, scientists have discovered that skin cells can become stem cells when they are dipped in acid, lowering the PH balance of the cell.

Stem cells can adapt to become almost any organ in the body, while other cells in the body have a particular purpose, such as liver or heart. So, by bypassing such controversial methods as the use of embryonic stem cells, the near future could hold a much faster, more personalized use of stem cells in many areas of medicine.

These initial findings have been compiled with research from mice, and the research is now being carried over into the human realm. While the new findings have a way to go before being directly beneficial to patients, once the stem cell research therapies are established, these new findings will make it much more accessible.

You can read more about the basic science of stem cell research on Medical News Today.

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therapy treatment for stem cell therapy treatment for cerebral palsy by dr alok sharma, mumbai, – Video

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therapy treatment for stem cell therapy treatment for cerebral palsy by dr alok sharma, mumbai,
improvement seen in just 5 days after stem cell therapy treatment for cerebral palsy by dr alok sharma, mumbai, india. Stem Cell Therapy done date 31 Dec 201...

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Split Decision: Stem Cell Signal Linked with Cancer Growth

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Newswise Researchers at the University of California, San Diego School of Medicine have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new target for treating leukemia because cancer stem cells rely upon the same protein to regulate and sustain their growth.

Hematopoietic stem cells give rise to all other blood cells. Writing in the February 2, 2014 advance online issue of Nature Genetics, principal investigator Tannishtha Reya, PhD, professor in the Department of Pharmacology, and colleagues found that a protein called Lis1 fundamentally regulates asymmetric division of hematopoietic stem cells, assuring that the stem cells correctly differentiate to provide an adequate, sustained supply of new blood cells.

Asymmetric division occurs when a stem cell divides into two daughter cells of unequal inheritance: One daughter differentiates into a permanently specialized cell type while the other remains undifferentiated and capable of further divisions.

This process is very important for the proper generation of all the cells needed for the development and function of many normal tissues, said Reya. When cells divide, Lis1 controls orientation of the mitotic spindle, an apparatus of subcellular fibers that segregates chromosomes during cell division.

During division, the spindle is attached to a particular point on the cell membrane, which also determines the axis along which the cell will divide, Reya said. Because proteins are not evenly distributed throughout the cell, the axis of division, in turn, determines the types and amounts of proteins that get distributed to each daughter cell. By analogy, imagine the difference between cutting the Earth along the equator versus halving it longitudinally. In each case, the countries that wind up in the two halves are different.

When researchers deleted Lis1 from mouse hematopoietic stem cells, differentiation was radically altered. Asymmetric division increased and accelerated differentiation, resulting in an oversupply of specialized cells and an ever-diminishing reserve of undifferentiated stem cells, which eventually resulted in a bloodless mouse.

What we found was that a large part of the defect in blood formation was due to a failure of stem cells to expand, said Reya. Instead of undergoing symmetric divisions to generate two stem cell daughters, they predominantly underwent asymmetric division to generate more specialized cells. As a result, the mice were unable to generate enough stem cells to sustain blood cell production.

The scientists next looked at how cancer stem cells in mice behaved when the Lis1 signaling pathway was blocked, discovering that they too lost the ability to renew and propagate. In this sense, the effect Lis1 has on leukemic self-renewal parallels its role in normal stem cell self-renewal, Reya said.

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