New Stem Cell Gene Therapy Gives Hope to Prevent Inherited Neurological Disease

Source: University of Manchester
Date: 25 July 2013

Summary:

Scientists from The University of Manchester have used stem cell gene therapy to treat a fatal genetic brain disease in mice for the first time.  The method was used to treat Sanfilippo – a fatal inherited condition which causes progressive dementia in children – but could also benefit several neurological, genetic diseases.  Researchers behind the study, published in the journal Molecular Therapy this month, are now hoping to bring a treatment to trial in patients within two years.

Stem Cell Researchers Use Gene Therapy to Restore Immune Systems in 'Bubble Boy' Disease

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: September 11, 2012

Summary:

UCLA stem cell researchers have found that a gene therapy regimen can safely restore immune systems to children with so-called "Bubble Boy" disease, a life threatening condition that if left untreated can be fatal within one to two years.

In the 11-year study, researchers were able to test two therapy regimens for 10 children with ADA-deficient severe combined immunodeficiency (SCID). During the study, they refined their approach to include a light dose of chemotherapy to help remove many of the blood stem cells in the bone marrow that are not creating an enzyme called adenosine deaminase (ADA), which is critical for the production and survival of healthy white blood cells, said study senior Dr. Donald Kohn, a professor of pediatrics and of microbiology, immunology, and molecular genetics in Life Sciences and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The refined gene therapy and chemotherapy regimen proved superior to the other method tested in the study, restoring immune function to three of the six children who received it, Kohn said. Going forward, an even further refined regimen using a different type of virus delivery system will be studied in the next phase of the study, which already has enrolled eight of the 10 patients needed.

The study appears Aug. 30 in the advance online issue of the peer-reviewed journal Blood.

New Genetic Mechanism for Controlling Blood Cell Development and Blood Vessel Integrity Found

Source: University of Wisconsin-Madison
Date: September 10, 2012

Summary:

The protein GATA2 is known as a "master regulator" of blood cell development. When a mutation occurs in the gene that makes GATA2, serious blood diseases such as acute myeloid leukemia can result. Zooming in on the GATA2 gene, University of Wisconsin-Madison researchers and their collaborators at the National Institutes of Health (NIH) have discovered unexpectedly that a small DNA sequence drives this powerful master regulator. The sequence plays an essential role in controlling GATA2 production and generating self-renewing blood stem cells responsible for the earliest steps in the development of blood cells of all kinds — red cells to transport oxygen and white cells to fight infection.

The researchers also found that the DNA sequence, which they call the +9.5 GATA2 switch site, ensures that blood vessels function properly to prevent hemorrhaging. Until now, GATA2 had not been implicated in blood vessel integrity. The study appears in The Journal of Clinical Investigation (online Sept. 10, 2012).

First Lung Cells Grown Using Stem Cell Technology

Source: The Hospital for Sick Children (SickKids)
Date: August 26, 2012

Summary:

New stem cell research paves the way towards individualized medicine for patients with cystic fibrosis and other lung diseases. The study, led by The Hospital for Sick Children (SickKids), is the first to successfully use stem cells to produce mature lung cells that could potentially be used to study the disease and test drugs. The study is published in the August 26 advance online edition of Nature Biotechnology.

Researchers were able to induce human embryonic stem cells to become mature lung cells, that contained a gene, called CFTR that when mutated is responsible for cystic fibrosis (CFTR gene was discovered at SickKids in 1989). They then took the experiment a step further, by using induced pluripotent stem cells derived from the skin of patients with cystic fibrosis. They prompted these stem cells to become lung cells, which contain mutations specific to the patients involved. (Induced pluripotent stem cells are adult cells genetically induced to function like embryonic stem cells.)

Once researchers found that they could create lung cells derived from individual patients they then used a compound that resembles an investigational drug that is currently being tested for cystic fibrosis to see if it would rescue the CFTR gene mutation.

The Winnipeg Free Press published a news story today on this development.

New Treatment Target for Deadly Brain Tumors

Source: University of Texas Southwestern Medical Center
Date: August 1, 2012

Summary:

A study by UT Southwestern Medical Center researchers published August 1 in Nature reveals new insight into why the most common, deadly kind of brain tumor in adults recurs and identifies a potential target for future therapies.

Glioblastoma multiforme (GBM) currently is considered incurable. Despite responding to initial therapy, the cancer almost always returns. GBM is a fast-growing, malignant brain tumor that occurred in 15 percent of the estimated 22,000 Americans diagnosed with brain and nervous system tumors in 2010. The median survival rate is about 15 months, according to the National Cancer Institute. Using a genetically engineered mouse model of GBM, the researchers found that the resting tumor cells act more like stem cells -- the non-cancerous cells the body uses to repair and replenish itself,

Speeding Up Bone Growth by Manipulating Stem Cells

Source: University of South Carolina
Date: June 22, 2012

Summary:

A researcher at the University of South Carolina, has made significant progress toward reducing the time for broken bone to heal. A study published in Molecular Pharmaceutics found that surfaces coated with bionanoparticles could greatly accelerate the early phases of bone growth. Their coatings, based in part on genetically modified Tobacco mosaic virus, reduced the amount of time it took to convert stem cells into bone nodules -- from two weeks to just two days.

The conversion of these cells -- called stem cells -- is set into motion by external cues. In bone healing, the body senses the break at the cellular level and begins converting stem cells into new bone cells at the location of the break, bonding the fracture back into a single unit. The process is very slow, which is helpful in allowing a fracture to be properly set, but after that point the wait is at least an inconvenience, and in some cases highly detrimental. The researchers found that the coatings alone could reduce the amount of time to grow bone nodules from stem cells. Since then, theyhave refined their approach to better define just what it is that accelerates bone growth.

Scientists Reprogram Skin Cells Into Brain Cells

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

Scientists at the Gladstone Institutes have for the first time transformed skin cells -- with a single genetic factor -- into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation -- or reprogramming -- of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

This research comes at a time of renewed focus on Alzheimer's disease, which currently afflicts 5.4 million people in the United States alone -- a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

Scientists Reprogram Skin Cells into Brain Cells Innovative technique lays groundwork for novel stem cell therapies

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

SAN FRANCISCO, CA—Scientists at the Gladstone Institutes have for the first time transformed skin cells—with a single genetic factor—into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation—or reprogramming—of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

In findings appearing online today in Cell Stem Cell, researchers in the laboratory of Gladstone Investigator Yadong Huang, MD, PhD, describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

The Real Culprit Behind Hardened Arteries? Stem Cells, Says Landmark Study

Source: University of California - Berkeley
Date: June 6, 2012

Summary:

BERKELEY — One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit. The UC Berkeley researchers say that these newly discovered stem cells contribute to artery-hardening vascular diseases that can lead to heart attacks and strokes.

The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.

Instead, a previously unknown type of stem cell — a multipotent vascular stem cell — is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing June 6 in the journal Nature Communications.

Mechanism That Maintains Stem Cells Readiness Identified

Source: University of Texas Southwestern Medical Center
Date: May 31, 2012

Summary:

An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at University of Texas Southwestern Medical Center report today in the journal Nature.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car’s brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don’t use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells’ other major activity, Dr. Zhang said. He stressed that the inhibition doesn’t cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors’ action only in leukemia.

Scientists Find Neural Stem Cell Regulator

Source: University of Colorado Denver
Date: April 16, 2012

Summary:

Researchers at the University of Colorado School of Medicine have found that lack of a specific gene interrupts neural tube closure, a condition that can cause death or paralysis. The study was the cover story this week in the journal Genes & Development.

The researchers made their findings while studying neural stem cells in mice. They said the cells use distinct self-renewal programs to meet the demand of tissue growth and repair during different stages of embryonic development. The molecular mechanisms that control these programs remain largely unknown. The researchers discovered that the gene mLin41 in mice controls the extent of neural stem cell proliferation during the process of neural closure but not at the later stage of brain development.

Big Advance Against Cystic Fibrosis: Stem Cell Researchers Create Lung Surface Tissue in a Dish

Source: Massachusetts General Hospital
Date: April 5, 2012

Summary:

Harvard stem cell researchers at Massachusetts General Hospital (MGH) have taken a critical step in making possible the discovery in the relatively near future of a drug to control cystic fibrosis (CF), a fatal lung disease that claims about 500 lives each year, with 1,000 new cases diagnosed annually.

Beginning with the skin cells of patients with CF, Jayaraj Rajagopal, MD, and colleagues first created induced pluripotent stem (iPS) cells, and then used those cells to create human disease-specific functioning lung epithelium, the tissue that lines the airways and is the site of the most lethal aspect of CF, where the genes cause irreversible lung disease and inexorable respiratory failure.

That tissue, which researchers now can grow in unlimited quantities in the laboratory, contains the delta-508 mutation, the gene responsible for about 70 percent of all CF cases and 90 percent of the ones in the United States. The tissue also contains the G551D mutation, a gene that is involved in about 2 percent of CF cases and the one cause of the disease for which there is now a drug.

The work is featured on the cover of this month's Cell Stem Cell journal. Postdoctoral fellow Hongmei Mou, PhD, is first author on the paper, and Rajagopal is the senior author.

New Approach to Treating Type I Diabetes? Scientists Transform Gut Cells into Insulin Factories

Source: Columbia University Medical Center
Date: March 12, 2012

Summary:

A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections. The research -- conducted in mice -- was published 11 March 2012 in the journal Nature Genetics.

The study shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. The insulin made by the gut cells also was released into the bloodstream, worked as well as normal insulin, and was made in sufficient quantity to nearly normalize blood glucose levels in otherwise diabetic mice.

Researchers Develop Gene Therapy to Boost Brain Repair for Demyelinating Diseases

Source: California Institute of Technology
Date: February 8, 2012

Summary:

Our bodies are full of tiny superheroes—antibodies that fight foreign invaders, cells that regenerate, and structures that ensure our systems run smoothly. One such structure is myelin—a material that forms a protective, insulating cape around the axons of our nerve cells so that they can send signals quickly and efficiently. But myelin, and the specialized cells called oligodendrocytes that make it, become damaged in demyelinating diseases like multiple sclerosis (MS), leaving neurons without their myelin sheaths. As a consequence, the affected neurons can no longer communicate correctly and are prone to damage. Researchers from the California Institute of Technology (Caltech) now believe they have found a way to help the brain replace damaged oligodendrocytes and myelin. The therapy, which has been successful in promoting remyelination in a mouse model of MS, is outlined in a paper published February 8 in The Journal of Neuroscience.

The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models. According to the researchers, LIF enables remyelination by stimulating oligodendrocyte progenitor cells to proliferate and make new oligodendrocytes.

Study finds iPS cells match embryonic stem cells in modeling human disease

Source: Stanford University School of Medicine
Date: December 12, 2011

Summary:

Stanford University School of Medicine investigators have shown that iPS cells, viewed as a possible alternative to human embryonic stem cells, can mirror the defining defects of a genetic condition — in this instance, Marfan syndrome — as well as embryonic stem cells can. An immediate implication is that iPS cells could be used to examine the molecular aspects of Marfan on a personalized basis. Embryonic stem cells, on the other hand, can’t do this because their genetic contents are those of the donated embryo, not the patient’s.

This proof-of-principle regarding the utility of induced pluripotent stem cells also has more universal significance, as it advances the credibility of an exciting approach that’s been wildly acclaimed by some and viewed through gimlet eyes by others: the prospect of using iPS cells in modeling a broad range of human diseases. These cells, unlike ESCs, are easily obtained from virtually anyone and harbor a genetic background identical to the patient from which they were derived. Moreover, they carry none of the ethical controversy associated with the necessity of destroying embryos.

The study was published online Dec. 12 in Proceedings of the National Academy of Sciences.

Research could help people with declining sense of smell

Source: University of California - Berkeley
Date: December 7, 2011

Summary:

University of California, Berkeley, neuroscientists have discovered a genetic trigger that makes the nose renew its smell sensors, providing hope for new therapies for people who have lost their sense of smell due to trauma or old age. The gene tells olfactory stem cells ‑ the adult tissue stem cells in the nose ‑ to mature into the sensory neurons that detect odors and relay that information to the brain. The discovery may also help scientists harness olfactory stem cells and stem cells found in other sensory systems more generally, to recover sensory function following injury or degenerative disease, scientists said. The findings are published in the Dec. 8 issue of the journal Neuron.

researchers identify new method for generating stem cell-like cells from human skin

Source: University of California - Los Angeles
Date: December 1, 2011

Summary:

Researchers from the UCLA School of Dentistry investigating how stem cells can be used to regenerate dental tissue have discovered a way to produce cells with stem cell–like characteristics from the most common type of human skin cell in the epidermis. These skin cells, called keratinocytes, form the outermost layer of skin and can be cultured from discarded skin tissues or biopsy specimens. The findings, published in the Nov. 4 edition of the peer-reviewed Journal of Biological Chemistry, may be beneficial for individuals with limited sources of endogenous stem cells.

Gene Therapy Shows Promise as Hemophilia Treatment in Animal Studies

Source: Wake Forest Baptist Medical Center
Date: November 3, 2011

Summary:

WINSTON-SALEM, N.C. – – For the first time, researchers have combined gene therapy and stem cell transplantation to successfully reverse the severe, crippling bleeding disorder hemophilia A in large animals, opening the door to the development of new therapies for human patients. Researchers at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine, collaborating with other institutions, report in Experimental Hematology that a single injection of genetically-modified adult stem cells in two sheep converted the severe disorder to a milder form.

Clean Correction of a Patient's Genetic Mutation New gene therapy methods accurately Correct mutation in patient's stem cells

Source: Wellcome Trust Sanger Institute
Date: 12 October 2011

Summary:

For the first time, scientists have cleanly corrected a human gene mutation in a patient's stem cells. The result, reported in Nature 12 October, brings the possibility of patient-specific therapies closer to becoming a reality. The team, led by researchers from the Wellcome Trust Sanger Institute and the University of Cambridge, targeted a gene mutation responsible for both cirrhotic liver disease and lung emphysema. Using cutting-edge methods, they were able to correct the sequence of a patient's genome, remove all exogenous DNA and show that the corrected gene worked normally.

CORRECTING SICKLE CELL DISEASE WITH STEM CELLS

Source: Johns Hopkins Medical Institutions
Date: September 28, 2011

Summary:

Using a patient’s own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene. The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for SCD and a variety of other blood disorders.

In an article published online August 31 in Blood, the researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD, which is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. People who inherited two copies — one from each parent — of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage and premature death.