Disease Focus: Liver Disease
Assessing the Functional, Immunologic and Microbiologic Characteristics of Human Livers Created in Chimeric Pigs
Research Objective Generating human liver using pig as a bioreactor Impact The livers produced will be used for transplantation into patients with end-stage liver disease, metabolic disorders, and for metastatic liver disease not amenable to resection Major Proposed Activities MILESTONE 1 TASKS 1) Procure liver from control pig 2) Place on XVIVO Perfusion Device MILESTONE […]
iPSCs as a screening tool to predict risk of nonalcoholic fatty liver disease
Research Objective The objective of this proposal is to established undifferentiated iPSCs as a diagnostic tool for the prediction of nonalcoholic fatty liver disease onset and severity. Impact Despite the widespread estimated prevalence of NAFLD, there are currently no tools available to predict likelihood of NAFLD susceptibility beyond standard clinical and demographic information. Major Proposed […]
Universal Pluripotent Liver Failure Therapy (UPLiFT)
Research Objective Universal Pluripotent Liver Failure Therapy (UPLiFT) is composed of 2 lines- UPLiFT0 ( from LiPSC-GR1.1) and UPLiFT1 which will be derived from gene edited universal human pluripotent stem cells. Impact In some liver-based metabolic diseases, replacement of 5-10% of the liver mass may salvage the patient. Transplantation of hepatic progenitors from universal donor […]
Towards hepatocyte cell replacement therapy: developing a renewable source of human hepatocytes from pluripotent stem cells
Research Objective To develop a consistent and abundant source of transplantable human hepatocytes for transplantation. Impact Developing an abundant and consistent source of human hepatocytes that can be used to treat patients with liver failure. Major Proposed Activities To determine the degree by which human pluripotent stem cell (hPSC)-derived hepatocytes engraft and restore liver function […]
Preclinical development of AAV vector-mediated in vivo hepatic reprogramming of myofibroblasts as a therapy for liver fibrosis
Research Objective An intravenously injectable virus that converts the scar cells responsible for liver cirrhosis into the cells that provide most of the liver’s function, thereby preventing or reversing liver failure. Impact The proposed research will develop a new therapy for liver cirrhosis, which can be cured by liver transplantation, but there are not enough […]
Preclinical development of human hepatocyte progenitor cells for cell therapy
Research Objective Determine if human hepatocyte progenitor cells, which exist in the normal adult liver, can be maintained and expanded in vitro while maintaining in vivo regenerative capacity. Impact Cell transplantation therapy can be an effective alternative treatment for severe liver diseases to liver transplantation, which is severely limited by the lack of available donor […]
Generation of bile duct-competent transplantable human liver organoids
Research Objective Generation of human stem cell-derived mini livers capable of exporting bile into the gallbladder after transplantation into the liver Impact Mini livers capable of normal bile export would have potential for therapy of diseases in which bile export is impaired like Alagille syndrome Major Proposed Activities Generation of mini livers using human stem […]
Development of a clinical-grade extracorporeal liver support system using human induced pluripotent stem cell-derived hepatic cells
Liver failure is the fourth leading cause of adult death in California. Because liver cells can regenerate, some patients with liver failure could be saved without having to undergo organ transplantation if their liver function could be supported temporarily. Here, we propose to develop a device to support these patients called the “extracorporeal liver support […]
Gene therapy-corrected autologous hepatocyte-like cells from induced pluripotent stem cells for the treatment of pediatric single enzyme disorders
Liver transplantation (LT) has been used to treat a variety of liver diseases. Within hours after birth, neonates can present with disorders of the urea cycle (UCDs), the critical metabolic liver pathway needed to detoxify waste nitrogen from the diet and cellular turnover. The overall incidence of UCDs is estimated to be 1 in 8200 […]
Development of a cell and gene based therapy for hemophilia
Hemophilia B is a bleeding disorder caused by the lack of FIX in the plasma and affects 1/30,000 males. Patients suffer from recurrent bleeds in soft tissues leading to physical disability in addition to life threatening bleeds. Current treatment (based on FIX infusion) is transient and plagued by increased risk for blood-borne infections (HCV, HIV), […]