Neuron cells have long finger-like structures, called axons, that extend outward to conduct impulses and transmit information to other neurons and muscle fibers. After spinal cord injury or stroke, axons originating in the brain’s cortex and along the spinal cord become damaged, disrupting motor skills. Now, reported today in Neuron, a team of scientists at Boston Children’s Hospital has developed a method to promote axon regrowth after injury. …
Getting a damaged optic nerve to regenerate is vital to restoring vision in people blinded through nerve trauma or disease. A variety of growth-promoting factors have been shown to help the optic nerve’s retinal ganglion cells regenerate their axons, but we are still far from restoring vision. A new study published yesterday in Neuron underscores the complexity of the problem.
A research team led by Fengfeng Bei, PhD, of Brigham and Women’s Hospital, Zhigang He, PhD, and Michael Norsworthy, PhD, of Boston Children’s Hospital, and Giovanni Coppola, MD, of UCLA conducted a screen for transcription factors that regulate the early differentiation of RGCs, when axon growth is initiated. While one factor, SOX11, appeared to be critical in helping certain kinds of RGCs regenerate their axons, it simultaneously killed another type — alpha-RGCS (above)— when tested in a mouse model.
At least 30 types of retinal ganglion cell message the brain via the optic nerve. “The goal will be to regenerate as many subtypes of neurons as possible,” says Bei. “Our results here suggest that different subtypes of neurons may respond differently to the same factors.”
If only there were a cure. David Breault, MD, PhD, associate chief of the Division of Endocrinology at Boston Children’s Hospital, was seeing patient after patient with Type I diabetes. Children facing lifetimes of insulin injections, special diets and the threat of long-term complications including blindness, heart disease and kidney failure.
Breault knew that patients with type I diabetes mysteriously destroy their own insulin-producing beta cells. He had read reports of researchers transplanting beta cells to supplement insulin. These transplants, even when successful, required powerful immunosuppressant medications to prevent patients’ immune systems from attacking the donor cells.
But Breault was also aware that investigators had, for a decade, been looking to stem cells as the source of a constantly renewing supply of beta cells. Advancing that promise, he has now found a way to convert patients’ own cells — from the stomach and intestine — into beta cells that produce insulin. …
Except when spreading awareness about her condition, 6-year-old Gianna DeCarlo prefers not to wear two-piece bathing suits because of the long vertical scar on her stomach. “Even though nobody’s said anything, she feels like she’ll be made fun of,” says her mother, Danielle. “I do what I can to make her love her body.”
Gianna doesn’t remember her three surgeries or the nasogastric tube she needed as an infant, before she was able to eat normally. She was born with gastroschisis, a striking birth defect in which the abdominal wall doesn’t seal fully during fetal development. As a result, her intestines developed outside her body. She was fed through an IV for several weeks, and was finally stitched fully shut at age 2. …
Could regenerative techniques restore hearing or balance by replacing lost sensory cells in the inner ear? Lab-created inner-ear organs, described today in Nature Communications, could provide helpful three-dimensional models for testing potential therapies.
The lab-built sac-like structure above, about 1 millimeter in size, contains fully-formed balance organs resembling the utricle and saccule, which sense head orientation and movement and send impulses to the brain. The tiny organs were built from mouse embryonic stem cells in a 3-D tissue culture in work led by Jeffrey Holt, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and Eri Hashino, PhD, of the University of Indiana. …
An anterior cruciate ligament (ACL) tear can be a devastating sports injury. Every year, 400,000 people, many of them teen and young adult athletes, sustain ACL injuries or tears. Martha Murray, MD, an orthopedic surgeon at Boston Children’s Hospital, worked with a team of colleagues to create a new procedure known as bridge-enhanced ACL repair (BEAR) that encourages natural healing. Watch this animation to see how it works:
Why do surgeons need a better way to repair ACL injuries?
The current standard of care, surgical ACL reconstruction, is a good solution. But it is linked with a 20 percent risk of re-tearing the ACL, and many young patients face an increased risk of arthritis. Instead of removing the torn ACL and replacing it with a tendon graft, the BEAR technique uses a special protein-enriched sponge to encourage the torn ends to reconnect and heal. The researchers have completed a 20-patient safety trial and are enrolling additional patients in a 200-patient clinical study.
Learn more about Murray’s research.
An occasional roundup of news items Vector finds interesting.
Blood-brain barrier on chip
The blood-brain barrier protects the brain against potentially damaging molecules, but its gate-keeping can also prevent helpful drugs from getting into the central nervous system. Reporting in PLoS One, a team at the Wyss Institute for Biologically Inspired Engineering describes a 3-D blood-brain barrier on a chip — a hollow blood vessel lined with living human endothelial cells and surrounded by a collagen matrix bearing human pericytes and astrocytes. …
Tears of the knee’s anterior cruciate ligament — or ACL — are on the rise in middle school and high school athletes. The current treatment involves grafting in a piece of tendon from elsewhere in the body. It works very well, but requires six months to two years of post-op rehabilitation to regain strength in the knee and the place where the tendon was taken from (often the hamstring). Plus, up to 80 percent of patients develop arthritis within 15 years of the procedure.
Roughly a year ago we told you about Yi Zhang, PhD — a stem cell biologist in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine — and his efforts to make a cloning technique called somatic cell nuclear transfer (SCNT) more efficient.
With SCNT, researchers take an egg cell and replace its nucleus with that of an adult cell (such as a skin cell) from another individual. The donated nucleus basically reboots an embryonic state, creating a clone of the original cell.
It’s a hot topic in both agriculture and regenerative medicine. SCNT-generated cells can be used to clone an animal (remember Dolly the sheep?) or produce embryonic stem (ES) cell lines for research. But it’s an inefficient process, producing very few animal clones or ES lines for the effort and material it takes.
Zhang’s team reported last year that they could boost SCNT’s efficiency significantly by removing an epigenetic roadblock that kept embryonic genes in the donated nucleus from activating in cloned cells. Now, in a new paper in Cell Stem Cell, Zhang and his collaborators report that they’ve extended their work to improve the efficiency of SCNT in human cells.
When genome-wide association studies (GWAS) first started appearing 10 years ago, they were heralded as the answer to connecting human genetic variation to human disease. These kinds of studies—which sift population-level genetic data—have revealed thousands of genetic variations associated with diseases, from age-related macular degeneration to obesity to diabetes.
However, thus far GWAS have largely come up short when it comes to finding new therapies. Few significant drug targets have come to light based on GWAS data (though some studies suggest that these studies could help drug makers find new uses for existing molecules).
Part of the problem may be that, until now, the right tools haven’t been available to exploit GWAS data. But a few recent studies—including two out of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center—have used GWAS data to identify therapeutically promising targets, and then manipulated those targets using the growing arsenal of gene editing methods.
Does this mean that GWAS’ day has finally come?