Children's stem cell work begins Quick Hits from Children's Hospital Boston
New view of asthma may offer a better treatment target
Lab-grown organs become clinical reality Bridge to a beating heart
This spring, the lab of George Daley, MD, PhD, was given the green light to begin attempts at creating human embryonic stem cells, the "master cells" that can give rise to any cell type in the body. Funded by private donations, Daley's ultimate goal is to create customized embryonic stem cells that match a patient's tissue type. These cells could then be used to make the specialized cells needed to treat blood diseases and other disorders.
"By using customized, genetically matched cells, we hope to eliminate the need for tissue matching and avoid the rejection problems that currently plague transplants," explains Daley, associate director of Children's Hospital Boston's Stem Cell Program.
The stem cells will be created from eggs and embryos from couples undergoing in vitro fertilization (IVF) treatments at Brigham and Women's Hospital. Normally, some eggs and embryos from IVF are of insufficient quality to achieve a pregnancy and are discarded. Under a protocol approved by Institutional Review Boards and Embryonic Stem Cell Research Oversight Committees at both hospitals, couples will be offered the chance to donate them for research purposes. As Daley's team learns more about how stem cells form and behave, it will seek to generate embryonic stem cells using healthy eggs and patients' own cells.
In a recent study of 6 to 12-year-olds, David Bickham, PhD, and Michael Rich, MD, MPH, found that children who spent more time viewing violent television spent less time with friends, compared to children who watched non-violent television. Also, children who made television watching a social activity with friends spent a good deal of social time away from the TV, while those who watched alone spent less time doing other social activities with their friends.
Tracy Richmond, MD, and colleagues found that in general, black and Hispanic girls are less physically active than white girls, but there is only a negligible ethnic difference in boys' activity levels. The study also found that schools are a factor: within the same school, girls reported similar activity levels, regardless of race. It's unknown whether this is the result of differences in school income levels, resources and amount of physical education programming, or a reflection of neighborhood, social and cultural factors.
A study by otolaryngologist Dwight Jones, MD, and Brigham and Women's Hospital colleague Neil Bhattacharyya, MD, found that children living with smokers had significantly more airway complications after surgery, including excessive mucus secretion, constriction of the larynx or bronchial tubes and airway obstruction. The study followed 405 children having day surgical procedures, including 168 from households with smokers, and found that the more cigarettes smoked in the home, the more severe the complications. Some children exposed to cigarette smoke needed bronchodilators and extra oxygen, while some had to be kept overnight.
In one of the first Western-style molecular-level studies of traditional Eastern remedies, Nikolaus Sucher, MD, PhD, looked at 58 traditional Chinese medicines used to treat stroke and found that many formulations act in biological pathways known to be important in stroke. Interestingly, their success seems to be due to the combination of several elements, and not simply to one compound within the medicine. The pharmaceutical industry is starting to take a closer look at herbal medicines in the hope of finding new drugs.
David Bellinger, PhD, found that silver amalgam, used to fill cavities for over 150 years, poses no apparent risk to children. Amalgam is 50 percent mercury, a metal that can be toxic in large doses. However, when more than 500 children ages 6 to 10 were tracked for five years after receiving either amalgam or white composite fillings, there were no significant differences between the two groups in scores for IQ, memory, visual-motor function, renal function or in reporting of adverse health events.
Students from low-income families tend to score lower on the Massachusetts Comprehensive Assessment System (MCAS), the test required of all public schoolchildren in the state. Psychologist Deborah Waber, PhD, recently did a pilot study of 91 Boston fifth-graders that suggests that poverty-related factors—poor nutrition, exposure to violence or toxic agents and disorganized or stressful environments—can disrupt the development of "executive" brain functions like organization, planning and control over thoughts and actions. Waber believes measures like smaller classrooms in younger grades, teaching of organizational skills and use of special-education techniques would help improve executive functioning.
A newly recognized type of cell may be key in causing asthma, perhaps explaining why current therapies sometimes fail, according to Dale Umetsu, MD, PhD, and Omid Akbari, PhD, in Children's Hospital Boston's Division of Allergy and Immunology. Their discovery, published this year, is beginning to change how physicians view asthma, and may provide a better target for therapy.
Previously, the inflammatory process that is central to asthma was thought to be caused by type 2 helper T cells (Th2 cells). But in 2003, Umetsu and Akbari showed in mice that asthma development requires another group of immune cells called natural-killer T cells (NKT cells); mice without these cells did not develop airway hyperreactivity, a cardinal feature of asthma. And last February, Umetsu and a graduate student further showed that NKT-cell activation can produce asthma even in mice that have no Th2 cells.
Intrigued, Umetsu and Akbari decided to study human patients—14 adults with moderate to severe bronchial asthma. To their surprise, at least two-thirds of the T cells in the patients' lungs were NKT cells, not Th2 cells. In contrast, NKT cells were virtually absent in two control groups: six healthy people and five with sarcoidosis (an inflammatory disease affecting the lungs). These observations, published March 16 in The New England Journal of Medicine, strongly suggest that NKT cells play a prime role in human asthma.
"If we can specifically eliminate NKT cells, we should be able to treat asthma more effectively," Umetsu says. "Th2 cells may be less important than was thought."
When Anthony Atala, MD, undertook his research in tissue engineering at Children's Hospital Boston in 1990, he eyed a day when his patients would receive laboratory-grown organs created with their own cells.
That day has arrived, and for 15-year-old Lucas Massella and six other Children's patients, it couldn't have come soon enough.
Lucas was born with spina bifida, a congenital birth defect that causes incomplete closure of the spine and often results in poor bladder function. By age 5, he was completely incontinent, and as he got older he continued to suffer complications like bladder spasms, reflux and kidney infections. So at age 10, when his bladder failed and caused severe kidney damage, Lucas decided to take part in Atala's tissue-engineered bladder trial.
Atala fashioned new bladder tissue for Lucas from the outer muscle cells of the boy's own bladder, along with the urothelial cells that line the bladder walls. The cells were multiplied in the lab until there were enough to place on a specially constructed biodegradable scaffold shaped like a bladder. After seven to eight weeks in August 2001, a lab-grown bladder was surgically attached to Lucas's own.
As the new bladder tissue grew and integrated with his own bladder, Lucas's urinary incontinence markedly improved and his kidneys suffered no further damage. And because the bladder was grown from his own cells, tissue rejection was not a problem.
Lucas began to put his energy back into school and sports. Now in his sophomore year of high school, he's the South Central Connecticut wrestling champion and an honor student. He says, "The surgery has made my life easier. Being able to wrestle makes me feel good and I'm happier now."
This success is good news for the 10,000-plus children and adults each year who undergo bladder replacement or repair in the United States. The traditional operation uses tissue from the patient's gastrointestinal tract. But because the intestine is designed to absorb nutrients, whereas a bladder's role is to excrete, it often causes complications like osteoporosis, stone formation and, occasionally, cancer. Atala's patients had none of these complications.
Formal clinical trials of the lab-grown bladders are scheduled to begin later this year at several centers, including Children's.
Cell biologist Douglas Cowan, PhD, and his team have engineered tissue capable of passing electrical signals from the upper to the lower chambers of the heart in rats, potentially taking on the role of the defective atrioventricular (AV) node in complete heart block. The AV node synchronizes the beats of the heart's atria and ventricles. Without it, the heart can't pump blood efficiently. One in 22,000 babies is born with complete heart block each year.
A normal infant's heart beats 120 to 180 beats per minute, while that of a baby with comlpete heart block may beat as slowly as 40 to 80 beats per minute. Present treatment involves implantation of a pacemaker, but pacemakers fail over time and must be surgically replaced regularly. With a life expectancy of 70, a baby with complete heart block is likely to require 12 surgical procedures.
Cowan's team isolated muscle precursor cells called myoblasts and "seeded" them onto a collagen scaffolding, creating living tissue that could be implanted in the heart. In laboratory experiments with rats, the cells took on the properties of AV node cells, beating when electrically stimulated. Additionally, the muscle cells produced proteins called connexins that channel ions from cell to cell, connecting the cells electrically.
"The advantage of using myoblasts is that they can be taken from skeletal muscle rather than the heart itself, which will be important for newborns whose hearts are so tiny they cannot spare any tissue for a biopsy," Cowan says.
"We have a ways to go," he adds, "but if we can show that this works in humans, it will improve the quality of life for tens of thousands of babies."
To meet a baby who would benefit from this procedure, see the story on Angel Morales.