Friday, January 21 at 1:00pm to 1:45pm
For a Zoom link, please email firstname.lastname@example.org.
Johanna Ascher Bartlett, MD
Predictive Biomarkers of Progression of Acute Liver Failure in Children
Acute liver failure (ALF) affects healthy children of any age and is associated with a high mortality rate. Our hypothesis is that unique immune cell populations drive hepatocyte injury and progression of ALF in a singularly identifiable manner that correlates with patient outcomes. We have identified a cohort of 116 patients at CHLA who were hospitalized for ALF and will include those patients who have undergone liver biopsy during their illness. We will apply our novel liver-specific immune panel with 23 markers to generate highly detailed, dynamic single-cell data to characterize the immune landscape of pediatric ALF. Next, we will analyze and spatially map this data using our IMC pipeline to create a predictive model of patient outcomes in terms of spontaneous recovery, liver transplantation or death.
Kevin Collon, MD
Biodistribution of LV-TSTA Transduced Human Adipose-Derived Stem Cells Used for “Ex Vivo” Regional Gene Therapy for Bone Repair
Our study aims to determine the safety profile of human adipose-derived mesenchymal stem cells (hASCs) transduced ex vivo using a lentiviral vector carrying the cDNA for BMP-2 or eGFP, for treating critical sized femoral defects in an athymic rat model. Following organ harvest at successive timepoints post-implantation, we are evaluating the biodistribution of implanted hASCs and viral vectors using DNA isolation and ddPCR, as well as related organ toxicity using liver function tests and gross pathology. We will then evaluate for insertional mutagenesis and genotoxicity using integration site mapping. Preliminary results reveal decreasing numbers of cell and vector copies in defect implantation sites with each successive timepoint, with minimal signal in harvested organs starting at 4 days post-implantation, and no organ toxicity. Our results are consistent with long-term safety of hASC treatment in this model.
Allen Zhong, MD
PROM1+ Progenitor Cells Residing in Extrahepatic Bile Duct Peribiliary Glands Proliferate into Cholangiocytes in Response to Cholestatic Injury in Murine Biliary Atresia Models
Biliary Atresia is a congenital obliterative extrahepatic bile duct injury and the leading cause of pediatric liver failure. Prom1-expressing progenitor cells differentiate into intrahepatic cholangiocytes and are associated with worsening liver fibrosis. We hypothesized that Prom1- expressing progenitor cells exist in the peribiliary glands of the extrahepatic bile ducts and differentiate in response to injury. We demonstrated that a Prom1-expressing progenitor cell lineage repopulates the murine extrahepatic bile duct epithelium in a murine model, and that biliary organoids grown from murine extrahepatic bile ducts are universally comprised of a Prom1-expressing lineage. We conclude that Prom1-expressing progenitor cells promote EHBD epithelial repair, and this process may be disrupted in Biliary Atresia.