Status: Funded - Closed
Human mesenchymal stem cell therapy as a surgical treatment for necrotizing enterocolitis
Troy Markel, MD, FACS, FAAP
BACKGROUND: Necrotizing enterocolitis (NEC) is an intrabdominal emergency of the premature infant that often requires surgical intervention. The incidence ranges from 10-15% of preemies, and the mortality for the more severe cases of NEC reaches 50-60%. Those that require surgery will often have a large portion of intestine removed, which may preclude normal nutritional absorption.
GAP: There are currently no favorable medical treatments for necrotizing enterocolitis. Stem cells are a novel therapeutic alternative due to their angiogenic and reparative properties.
HYPOTHESIS: W hypothesize that: 1) Umbilical cord derived mesenchymal stem cells protect the intestine better than bone marrow derived mesenchymal stem cells or adipose derived mesenchymal stem cells, and 2) Mesenchymal stem cells provide their protective effects through the release of paracrine mediators.
METHODS: Intestinal ischemia will be induced in mice by temporarily occluding the superior mesenteric artery. Following ischemia, umbilical, bone marrow, or adipose derived MSCs or hypoxia conditioned acellular MSC media will be injected intraperitoneally. Animals will be assessed for survival and intestines will be assessed for inflammation, histology, motility, and permeability.
IMPACT: Only minor advancements have been made in the ability of clinicians to predict which infants will develop severe NEC. There is no current way to salvage the ischemic intestine identified at the time of surgery. The results from our preliminary data are encouraging, and may allow for the rescue or salvage of marginally appearing intestine. Saving even a few centimeters of intestine may mean the difference between long term parenteral nutrition and appropriate intestinal rehabilitation.