Cultured in a dish, stem cells spontaneously assembled themselves into a complex structure resembling an eye – a retina, to be exact.
SmartPlanet.com, April/May 2011, by Janet Fang — The discovery may help the development of eye disease treatments, such as stem cell-derived transplants for repair of the retina, which is lined with the light-sensing cells we need for vision.
It could one day provide an endless supply of cells for ‘the next generation of generative medicine in retinal degeneration therapeutics,’ according to the authors.
- First, scientists led by Yoshiki Sasai at the RIKEN Center for Developmental Biology grew floating clusters of embryonic stem cells from mice in a carefully crafted culture medium. The dish included proteins, like “a bandage to the tissue,” Sasai says. “Without that, cells tend to fall apart.”
- Over 12 days, the cells eventually organized themselves into a 3-D, layered structure reminiscent of an optic cup (pictured) – which forms the inner and outer layers of the retina during normal development.
The optic cup is brandy-snifter-shaped organ that has two distinct cell layers. The outer layer – that nearest to the brain – is made up of pigmented retinal cells that provide nutrients and support the retina. The inner layer is the retina itself, and contains several types of light-sensitive neuron, ganglion cells that conduct light information to the brain, and supporting glial cells.
The ‘retina in a dish’ is by far and away the most complex biological tissue engineered yet.
What’s so surprising about the self-directed organization of the stem cells is how the culture started as a patternless collection of cells that weren’t pushed or pressured to become any particular thing. The optic cup’s formation depends on some intrinsic, self-organizing program directing the fate and position of cells.
Though the optic cups may look and develop like the real thing, there may be differences between what’s synthetic and what happens normally. The team hasn’t shown if the optic cups can sense light or transmit impulses to the brain.
If the technique can be adapted to human retinas (which develop similarly to mouse ones) and proved safe for transplantation, it could offer an unlimited well of tissue to replace damaged retinas.
Retinitis pigmentosa and age-related macular degeneration are the most common causes of blindness in old age, and involve the gradual and normally irreversible destruction of retinal cells.
For now, retinas created from reprogrammed stem cells from patients with eye diseases could be used to screen drugs or test gene therapies.
The study was published on April 6, 2011 in Nature.
Image: optic cup in a test tube / M. Eiraku and Y. Sasai at RIKEN
UNDER PRESSURE: During Navy SEAL training in Coronado, Calif., students participate in a night gear exchange. Stress researcher George Everly has studied Navy SEALs and other resilient groups to identify distinct attributes of resiliency. Photo by Kyle D. Gahlau/U.S. Navy.
May 2011, by Karin Kiewra
Helping medical students manage stress
How do people maintain resiliency during stressful experiences? There’s no simple cure for the high rates of depression and burnout reported in recent studies of U.S. physicians, residents and medical students. But researchers who study stress and the brain say resiliency can be taught.
At the HMS Academy’s Seventh Annual Symposium on the Science of Learning on April 1, about 100 faculty members heard presentations on the topic of “Resiliency and Learning: Implications for Teaching Medical Students and Residents.”
“Understanding the neurological and psychological consequences of stress on learning and personal growth, good and bad, is critical as we work to optimize physician education,” said Richard Schwartzstein, director of the Academy, which works to advance medical education throughout the HMS community. Schwartzstein is the Ellen and Melvin Gordon Professor of Medical Education at Beth Israel Deaconess Medical Center.
Bruce McEwen, a professor of neuroendocrinology at the Rockefeller University, described evidence that brief episodes of acute stress can enhance memory and learning, while chronic, high levels can damage the mammalian brain.
Drawing on work with children and adults, George Everly, an associate professor of psychiatry at Johns Hopkins Bloomberg School of Public Health, plumbed the psychological roots of human resilience. Both he and McEwen cited a network of social support and faith in a higher power or purpose as key to bouncing back from trauma and intense, prolonged stress.
The Embattled Brain
Linking the nervous and endocrine systems, biochemical mediators regulate the effects of stress, which are exacerbated by health-related behaviors such as inactivity or poor diet. Under acute stress—think “fight or flight”—the hypothalamus churns out corticotropin-releasing hormone, prompting a sharp rise in the stress hormone cortisol, which enhances immunity, memory, energy and cardiovascular function. Once the stressor has passed, the hormone DHEA, neuropeptide Y and other biochemicals rush in, restoring equilibrium and easing symptoms, such as hypertension. Acutely, these mediators, along with emotional engagement with a task, may enhance learning.
But when stress is chronic, cortisol erodes health. Immune suppression, hypertension, bone mineral loss, muscle wasting and metabolic disorders ensue. Within the hippocampus and amygdala, seats of memory and emotion, dendrites shrink and synapses vanish, McEwen has shown. Cognitive function declines, depression sinks in, the immune system weakens, and metabolism goes awry. In a study of medical students preparing for board exams, McEwen’s collaborators found that higher levels of perceived stress predicted poor mental flexibility and reduced functional connectivity in the prefrontal cortex.
The good news: These ill effects are reversible, McEwen said. Regular exercise returns the hippocampus to normal size and improves memory, for example, while mindfulness training reduces the amygdala’s volume and curbs anxiety. Many adult diseases could be prevented by reducing toxic stress in utero and in early childhood, he said.
The Resilient Psyche
In the wake of war, natural disasters and severe abuse, 15 to 20 percent of those affected suffer from post-traumatic stress disorder. By focusing on the rest, including Navy SEALs and other stress-hardy groups, Everly has identified distinct attributes. The best predictor of immunity to stress, he said, is a social support network. Optimism (including faith in a higher cause or power), perseverance (work ethic), responsibility and integrity also count.
As for why some people sink instead of swim, Everly emphasized two factors: A lack of perspective—stemming from inadequate preparation and tenacity—and a negative attitude.
Resilience can be taught, said Everly, who also directs the Resiliency Sciences Institutes at the University of Maryland. First, let people experience success: Assign them to a successful group. Second, create a surveillance system and safety net, and provide encouragement, mentoring and training. Finally, mitigate the impact of stress by promoting “self-efficacy”—the belief that we are agents of change. Everly noted, however, that one cannot “give” self-esteem; it must be earned through personal accomplishment in the face of a challenge. Calling for a cultural shift, he said, “We must reframe mistakes as opportunities for learning.”
This 2010 photo provided by Rob Summers shows Summers, center, receiving intensive physical therapy in Louisville, Ky. Summers was paralyzed below the neck in a 2006 car accident and in 2009, doctors decided to implant an electrical stimulator onto his spinal cord to try waking up his damaged nervous system. Summers is now able to stand and move during therapy sessions with the stimulator turned on. Photo: Courtesy Of Rob Summers/
GoogleNews.com, StamfordAdvocate.com, FORBES.com, May 19, 2011, by MARIA CHENG, LONDON — After Rob Summers was paralyzed below the chest in a car accident in 2006, his doctors told him he would never stand again. They were wrong.
Despite intensive physical therapy for three years, Summers’ condition hadn’t improved. So in 2009, doctors implanted an electrical stimulator onto the lining of his spinal cord to try waking up his damaged nervous system. Within days, Summers, 25, stood without help. Months later, he wiggled his toes, moved his knees, ankles and hips, and was able to take a few steps on a treadmill.
“It was the most incredible feeling,” said Summers, of Portland, Oregon. “After not being able to move for four years, I thought things could finally change.”
Still, despite his renewed optimism, Summers can’t stand when he’s not in a therapy session with the stimulator turned on, and he normally gets around in a wheelchair. Doctors are currently limiting his use of the device to several hours at a time.
His case is described in a paper published Friday in the journal, Lancet. The research was paid for by the U.S. National Institutes of Health and the Christopher and Dana Reeve Foundation.
For years, certain people with incomplete spinal cord injuries, who have some control of their limbs, have experienced some improvement after experiments to electrically stimulate their muscles. But such progress had not been seen before in someone with a complete spinal cord injury.
“This is not a cure, but it could lead to improved functionality in some patients,” said Gregoire Courtine, head of experimental neurorehabilitation at the University of Zurich. He was not connected to Summers’ case. Courtine cautioned Summers’ recovery didn’t make any difference to the patient’s daily life and that more research was needed to help paralyzed people regain enough mobility to make a difference in their normal routines.
The electrical stimulator surgeons implanted onto Summers’ spinal cord is usually used to relieve pain and can cost up to $20,000. Summers’ doctors implanted it lower than normal, onto the very bottom of his vertebrae.
“The stimulator sends a general signal to the spinal cord to walk or stand,” said Dr. Susan Harkema, rehabilitation research director at the Kentucky Spinal Cord Injury Research Center in Louisville and the Lancet study’s lead author.
Harkema and her colleagues were surprised Summers was able to voluntarily move his legs. “That tells us we can access the circuitry of the nervous system, which opens up a whole new avenue for us to address paralysis,” Harkema said. She said prescribing drugs might also speed recovery.
Dr. John McDonald, director of the International Center for Spinal Cord Injury at Kennedy Krieger Institute in Baltimore, said the strategy could be rapidly adopted for the 10 to 15 percent of paralyzed patients who might benefit. He was not connected to the Summers case.
“There is no question we will do this for our patients,” he said. McDonald added that since the electrical stimulators are already approved for pain relief, it shouldn’t be difficult to also study them to help some patients regain movement.
For now, Summers does about two hours a day of physical therapy.
“My ultimate goal is to walk and run again,” he said. “I believe anything is possible and that I will get out of my wheelchair one day.”
SmartPlanet.com, May 19, 2011, by Janet Fang — It’s called a Van Nes Rotationplasty, and it preserved a rare cancer patient’s ability to play baseball.
After 12-year-old Dugan Smith was diagnosed with osteosarcoma – and a tumor on his thighbone – he had the option of having the diseased bone replaced with a cadaver bone or a manmade rod. Or it could be amputated altogether.
But instead, the doctors from Ohio State University Medical Center did the following:
- Cut off the middle part of the leg (including the knee and most of the thigh).
- Remove the tumor from the femur (thighbone).
- With the nerves still connected, turn the bottom part of the leg around 180 degrees.
- Reconnect the blood vessels.
- Then sew the lower half of the leg onto his hip – again, backwards – making the calf act as the thigh and the ankle act as his knee (pictured). The foot faces, well, backwards.
Within two hours, he could move his foot and toes – which slid into a partial prosthetic leg and foot to compensate for the missing lower half of the right leg.
According to the team, an amputation above the knee would require about 75% more energy to walk or run than with a normal leg. With the leg reversal surgery, it would take only about 30% more energy, and it also decreases the chances of a tumor recurrence.
Risks from the surgery include a danger of clots developing when reconnecting the blood supply, infection, and damage to the nerves when twisting and stretching the leg. Only about a dozen rotationplasties are performed in the US a year.
Images: Ohio State University