New tools and technologies fueled biomedicine to great heights in 2017. Here are just a few of our top picks. All are great examples of research informing better care for children (and adults).
1. Gene therapy arrives
In 2017, gene therapy solidly shed the stigma of Jesse Gelsinger’s 1999 death with the development of safer protocols and delivery vectors. Though each disease must navigate its own technical and regulatory path to gene therapy, the number of clinical trials is mounting worldwide, with seven gene therapy trials now recruiting at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. In August, the first gene therapy won FDA approval: CAR T-cell therapy for pediatric acute lymphoblastic leukemia. …
The amniotic fluid surrounding babies in the womb contains fetal mesenchymal stem cells (MSCs) that can differentiate into many cell types and tissues. More than a decade ago, Dario Fauza, MD, PhD, a surgeon and researcher at Boston Children’s Hospital, proposed using these cells therapeutically. His lab has been exploring these cells’ healing properties ever since.
Replicated in great quantity in the lab and then reinfused into the amniotic fluid in animal models — a reverse amniocentesis if you will — MSCs derived from amniotic fluid have been shown to repair or mitigate congenital defects before birth. In spina bifida, they have induced skin to grow over the exposed spinal cord; in gastroschisis, they have reduced damage to the exposed bowel. Fauza calls this approach Trans-Amniotic Stem Cell Therapy, or TRASCET.
For a tissue graft to survive in the body — whether it’s a surgical graft or bioengineered tissue — it needs to be nourished by blood vessels, and these vessels must connect with the recipient’s circulation. While scientists know how to generate blood vessels for engineered tissue, efforts to get them to connect with the recipient’s vessels have mostly failed.
“Surgeons will tell you that when putting tissue in a new location in the body, the small blood vessels don’t connect at the new site,” says Juan Melero-Martin, PhD, a researcher in Cardiac Surgery in Boston Children’s Hospital. “If you want to engineer a tissue replacement, you’d better understand how the vessels get connected, because if the vessels go, the graft goes.”
Melero-Martin and colleagues have uncovered several strategies to help these connections form, as they describe online today in Nature Biomedical Engineering. The strategies could help improve the success of such procedures as heart patching, bone grafting, fat transplants and islet transplantation. …
Gene therapy stalled in the early 2000s as adverse effects came to light in European trials (leukemias triggered by the gene delivery vector) and following the 1999 death of U.S. patient Jesse Gelsinger. But after 30 years of development, and with the advent of safer vectors, gene therapy is becoming a clinical reality. It falls into two main categories:
In vivo: Direct injection of the gene therapy vector, carrying the desired gene, into the bloodstream or target organ.
Ex vivo: Removal of a patient’s cells, treating the cells with gene therapy, and reinfusing them back into the patient, as in hematopoietic stem cell transplant and CAR T-cell therapy.
The care and feeding of more than 250,000 zebrafish just got better, thanks to a $4 million grant from the Massachusetts Life Sciences Center to upgrade Boston Children’s Hospital’s Karp Aquatics Facility. Aside from the fish, patients with cancer, blood diseases and more stand to benefit.
From a new crop of Boston-Children’s-patented spawning tanks to a robotic feeding system, the upgrade will help raise the large numbers of the striped tropical fish needed to rapidly identify and screen potential new therapeutics. It’s all part of the Children’s Center for Cell Therapy, established in 2013. We put on shoe covers and took a look behind the scenes. (Photos: Katherine Cohen) …
The neural tube, which becomes the spinal cord and brain, is supposed to close during the first month of prenatal development. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.
New research from Boston Children’s Hospital, though still in animal models, suggests that standard amniocentesis, followed by one or more injections of cells into the womb, could be enough to at least partially repair spina bifida prenatally.
Currently, the standard procedure is to operate on infants soon after delivery. …
Inflammatory bowel disease (IBD) is miserable for anyone, but when it strikes a child under age 5, it’s much more severe, usually causing bloody diarrhea, wrenching abdominal pain and stunted growth. Early-onset IBD is rare, but on the rise: For reasons unknown, its incidence is increasing by about 5 percent per year in some parts of the world.
A recently identified form of early-onset IBD shows up within months of birth, causing severe inflammation in the large intestine and abscesses around the anus. Recently linked to genetic mutations in the cellular receptor for a signaling protein, interleukin-10 (IL-10), it can also lead to lymphoma later in life.
As with all early-onset IBD, IL-10-receptor deficiency has no good treatment. A bone marrow transplant is actually curative, but carries many risks, especially in infants.
“We’ve been trying to understand why IBD in these children is so severe and presents so early,” says Dror Shouval, MD, a pediatric gastroenterologist at Boston Children’s Hospital and a fellow in the lab of Scott Snapper, MD, PhD. The beginnings of such an understanding—detailed recently in the journal Immunity—could lead to a new treatment approach for this and perhaps other kinds of early-onset IBD. …