The scientific wonder of stem cell research and its implications for medicine have come a long way in the last decade: At Children’s Hospital of Philadelphia Research Institute, our investigators’ innovative use of stem cell science to approach complex pediatric conditions continues to inspire for their potential to improve outcomes in children’s health. In our latest news roundup, learn about novel stem cell research from our Cancer Center and Division of Urology that aims to preserve the future fertility of boys who undergo childhood cancer treatment. Discover a new project co-led by a CHOP neurology researcher that takes a stem cell approach to restore vision cells in blind dogs. And stay updated on new breakthroughs in autism spectrum disorder (ASD) and childhood epilepsy, as our researchers learn more about the underlying genetics and associated conditions of each.
Novel Stem Cell Research Aims to Prevent Infertility in Childhood Cancer Survivors
Childhood cancer survivors experience a variety of long-term effects even after they have finished treatment, including fertility issues that stem from certain chemotherapies and radiation therapy that can kill the cells that produce sperm. In particular, many boys who undergo cancer treatment before they reach puberty are left infertile and currently have no existing options for fertility preservation. Jill Ginsberg, MD, a pediatric oncologist and director of our Cancer Survivorship Program at Children’s Hospital of Philadelphia, and Thomas Kolon, MD, a pediatric urologist at CHOP, recently collaborated with scientists at the Perelman School of Medicine at the University of Pennsylvania to conduct novel stem cell research that may open the door to new fertility preservation options for prepubescent boys.
Using human sperm-producing stem cells (SSCs) and animal models, the researchers discovered that endothelial cells from the testes are a viable environment for human SSCs to expand. Previously, scientists have had difficulty growing the immature SSCs in testis tissue to generate sufficient numbers to reinject back into a patient post-treatment. Drs. Ginsberg, Kolon, and their colleagues tested their recent findings in infertile male mice, and the mice were able to produce sperm and father offspring. The team published their findings in Nature Communications, and the research received coverage in Forbes and the Philly Voice.
CHOP Scientist Co-Leads Stem Cell Research to Restore Vision
With support from a new five-year, $6.9 million grant from the National Eye Institute, a multidisciplinary research team co-led by our own John H. Wolfe, PhD, VMD, a neurology researcher at CHOP, is working to develop stem cell-based approaches to restore vision in blind dogs.
“Our ultimate goal is to build the foundation for cell-based treatments to restore vision to people who have already lost key vision cells,” said Dr. Wolfe in a CHOP press release.
While existing gene therapies have had success in treating blindness, they cannot save areas of the retina where cells have already died. Working with scientists at the University of Pennsylvania and the University of Wisconsin-Madison, Dr. Wolfe’s research project “Retinal Disease Models for Translational Photoreceptor Placement” plans to reprogram cells taken from adult animals into stem cells, culture the stem cells in the lab into retinal photoreceptor cells, and then transfer the cells into the retinas of dogs with vision loss. The researchers will then determine how well the implanted cells function.
Dr. Wolfe is no stranger to testing and developing gene therapy approaches, particularly for neurological disorders: At CHOP, he has previously investigated gene therapy approaches to treating lysosomal storage disorders, which are caused by inherited defects that result in the absence or deficiency of an enzyme, leading to the inappropriate storage of material in various cells.
John Maris Featured in New York Academy of Sciences Podcast
Our own John Maris, MD, pediatric oncologist at CHOP, shared his insights last week on a New York Academy of Sciences (NYAS) podcast. The podcast episode “Finding Better Treatments for Children with Cancer” highlighted the latest advances in pediatric oncology research.
“If you look at the adult oncology landscape, there’s been this exponential increase in the number of FDA approvals for drugs ... but in childhood cancers, we’ve really lagged behind,” Dr. Maris states in the podcast.
Children with Autism Nearly 50 Percent More Likely to Be Overweight or Obese at 5 Years
Children with developmental delays, including autism spectrum disorder (ASD), are up to 50 percent more likely to be overweight or obese compared with the general population, according to collaborative new research from our Center for Autism Research (CAR), the University of Pennsylvania, and six other centers published in the Journal of Pediatrics. Furthermore, among children with ASD, those with a higher degree of impairment and more severe systems showed an even greater risk of developing obesity by the age of five.
“These findings make it clear that monitoring these children for excess weight gain at an early age is critical, and that prevention efforts should be expanded to include not just children with ASD, but those with other developmental diagnoses, as well,” said Susan E. Levy, MD, MPH, the study’s lead author and medical director of CAR, in a press release. Dr. Levy added that more research is needed to understand why children with developmental delays are more likely to develop obesity and which children are at the highest risk.
The large multisite study, which was a part of the Study to Explore Early Development (SEED), included nearly 2,500 children between 2 and 5 years old — a critical age window for early obesity prevention. Alongside obesity, the researchers also studied connections between excess weight gain and other medical, behavioral, developmental, or psychiatric conditions. Because other medical conditions are common among children with ASD, the researchers noted that these may play a role in excess weight gain.
Learn more in the press release.
New Causative Gene Discovered in Severe Childhood Epilepsy
An international research team that includes scientists from CHOP have discovered a new causative gene for a severe, difficult-to-treat childhood epilepsy syndrome that could offer clues to better treatment, publishing their findings in the American Journal of Human Genetics. The study, whose first author is Katherine L. Helbig, MS, CGC, a research genetic counselor in the Neurogenetics Program in the Division of Neurology, found that spontaneous mutations in the CACNAIE gene disrupt the flow of calcium in brain cells, resulting in epileptic overactivity.
According to Helbig, even though variants in the gene were only just discovered to cause disease, scientists already have a good understanding of how changes in the gene’s associated protein affect brain function. However, the current study is the first to link the CACNAIE gene to human epilepsy. Through next-generation sequencing, the researchers pinpointed disease-causing variants in CACNA1E in 30 infants and young children with severe epilepsy.
“The fact that we were able to identify 30 patients at this stage of research indicates that we could be looking at a more common cause of genetic epilepsy than we would have initially assumed,” said Helbig in a CHOP press release. “This research enables us to give some families an answer as to why their child has severe epilepsy. It also offers the potential that we can build on this knowledge to find new strategies for treatment.”
Read more about this research in the press release.
Recently on Cornerstone, we announced news about four scientists from our Cancer Center at CHOP who received grants from the St. Baldrick’s Foundation, published our latest Q&A with John Maris, MD, oncologist, on a new data release from the Pediatric Preclinical Testing Consortium and Alex’s Lemonade Stand Foundation, and shared highlights from PolicyLab’s “Charting New Frontiers in Children’s Health Policy and Practice” forum Oct.22.
Catch up on our headlines from our Oct. 19 edition of In the News:
- Scientific American Features Pediatric Sepsis Program Research
- Prenatal Gene Editing Shows Proof-of-Concept in Treating Congenital Disease
- Genomics Scientist Proposes New Model to Continuously Update Genetic Test Results
- Nature Features Top CHOP Genomics Scientists
- Genome-Wide Association Study Analysis Reveals New Insights into Type 1.5 Diabetes
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