The Besner Lab at Nationwide Children’s aims to eliminate necrotizing enterocolitis (NEC) and its downstream consequences. NEC is a devastating disease that primarily affects premature infants. In severe cases infants develop intestinal tissue necrosis, and surgical intervention is often required. Mortality exceeds 40% in low birth weight neonates, and there is a massive need for improvement in nearly every facet of NEC diagnosis and treatment. The Besner Lab conducts cutting-edge, novel research in both diagnosis and treatment.
Presently, there are no specialized treatments for NEC. Treatments are generally broad and focus on ameliorating symptomology. They can include gastric decompression, transfer from enteral feeds to total parenteral nutrition and broad-spectrum antibiotic treatment.
The Besner Lab has multiple lines of inquiry in how to improve NEC treatment:
Probiotics are bacteria that can exert beneficial health effects on the host. The Besner Lab and its collaborators have developed a probiotic delivery system that has demonstrated efficacy in significantly reducing NEC incidence in a rat pup NEC model. The system involved delivery of Lactobacillus reuteri in its biofilm state by incubation on biocompatible microspheres that can be loaded with beneficial cargo.
In addition to treating experimental NEC, this therapy can also treat Clostridium difficile colitis, and the Besner Lab continues to investigate its effects against other gastrointestinal diseases. Its team has also developed a piglet model of NEC to test the probiotic delivery system in a large animal model.
Survivors of NEC often have developmental delays in later life related to cognition and memory gaps. Another line of inquiry in the Besner Lab is how the probiotic supplement may ameliorate these delays. The lab has exciting evidence that delivery of Lactobacillus reuteri in its biofilm state protects the brain in survivors of NEC.
Exosomes are nanosized particles that are released by nearly every cell in the body. They are known to carry regulatory molecules from their parent cell which can act upon other cells elsewhere within the body.
The Besner Lab has been studying these molecules for their therapeutic potential. The team has isolated exosomes from both breast milk and stem cells and demonstrated that these exosomes are able to reduce NEC incidence in its rat pup NEC model.
In addition to having therapeutic qualities, exosomes can also be used as biomarkers for disease, given that they carry molecules from potential diseased cells. Presently, NEC infants present with similar symptoms as septic infants in the early stages, but disease treatment is unique between the two.
As with treatment, great improvement is needed in NEC diagnostics. The Besner Lab has been focused on characterizing the cargo molecules of exosomes from NEC patients and comparing them to molecules from babies with sepsis or otherwise healthy babies. By doing so, Dr. Besner and her lab members hope to identify molecules that are present in the exosomes of NEC patients that are more highly abundant than molecules from healthy or sepsis babies.
The Besner Lab is also developing tissue engineered intestine for the treatment of short bowel syndrome. The team has shown the ability to implant tissue engineered tissue in rats and are presently expanding this work into pigs.
Engineered tissue can be used for patients that have had significant portions of their intestines surgically resected, including infants with NEC and adults who undergo surgical remove of injured intestine.
Gail Besner, MD
Gail E. Besner, MD, principal investigator in the Center for Perinatal Research at the Abigail Wexner Research Institute at Nationwide Children's Hospital, is the chief of Pediatric Surgery and the associate program director of the Pediatric Surgery Residency program at Nationwide Children’s. She is also a professor of Surgery and Pediatrics at The Ohio State University College of Medicine, where she holds the H. William Clatworthy Jr. Professorship in Surgery.
Dr. Besner's clinical interests include neonatal surgery, necrotizing enterocolitis and pediatric burn care. Her research interests involve the identification of novel strategies to protect the intestines from injury using growth factors and stem cells, as well as the production of tissue engineered intestine. Dr. Besner's research has been funded by grants from the National Institutes of Health for over two decades.
Belgacem Mihi, DVM, PhD, is a research scientist in the Besner Lab. Dr. Mihi’s research interests include tissue engineering, epithelial cell biology and intestinal inflammation, and his current work focuses on understanding the molecular mechanisms behind the development of necrotizing enterocolitis in rodent and swine models to set the stage for translation into new human therapeutics. In addition, he is currently developing and optimizing new methods to generate ex vivo engineered human intestine.
Nitin is a general surgery resident from the Cleveland Clinic Foundation. She joins the Besner Lab team for a two-year research fellowship at Nationwide Children’s. Her interests include pediatric surgery and necrotizing enterocolitis.
Chief Research Associate / Lab Animal Coordinator
Yijie performs experiments using prophylactic and therapeutic agents, such as stem cells, probiotics and exosomes in rodent and swine NEC models and participates projects to generate tissue engineered small intestines. Yijie also writes/updates IACUC and IRB protocols in the Besner Lab, maintains lab mouse colonies, trains new lab members, maintains the lab’s supplies and budget, and supports its daily operation.
Samuel Grant Volpe
Samuel’s daily responsibilities in the Besner Lab include surgeries on mice and rats, data compilation/analysis, probiotic preparation, necropsy/dissections, tissue collection, histological analysis, organoid culturing, stem cell isolation, general laboratory maintenance and protocol development. He graduated from The Ohio State University with a degree in neuroscience.