Donor cell engineering with GSK3 inhibitor–loaded nanoparticles enhances engraftment after in utero transplantation

Host cell competition is a major barrier to engraftment after in utero hematopoietic cell transplantation (IUHCT). Here we describe a cell-engineering strategy using glycogen synthase kinase-3 (GSK3) inhibitor–loaded nanoparticles conjugated to the surface of donor hematopoietic cells to enhance their proliferation kinetics and ability to compete against their fetal host equivalents. With this approach, we achieved remarkable levels of stable, long-term hematopoietic engraftment for up to 24 weeks post-IUHCT. We also show that the salutary effects of the nanoparticle-released GSK3 inhibitor are specific to donor progenitor/stem cells and achieved by a pseudoautocrine mechanism. These results establish that IUHCT of hematopoietic cells decorated with GSK3 inhibitor–loaded nanoparticles can produce therapeutic levels of long-term engraftment and could therefore allow single-step prenatal treatment of congenital hematological disorders

Management of choledocholithiasis in an infant

Choledocholithiasis is a rare diagnosis in the infant population with poorly defined optimal management. Endoscopic and operative interventions are both technically challenging. Endoscopic retrograde cholangiopancreatography (ERCP), common bile duct exploration and laparoscopic cholecystectomy are typically safe and successful when performed. However, choledocholithiasis has been reported to spontaneously resolve in up to 60% of cases in neonates and infants. We present five cases of choledocholithiasis in infants and a comprehensive review of the literature. Based on our review and experience, we make a recommendation that clinicians should proceed with a selective approach in the management of this disease based on severity of symptoms, co-morbidities, and the available surgical and endoscopic capabilities of each institution