Novel cell therapies for liver disease and type 1 diabetes

Liver disease and type 1 diabetes affect millions, yet whole-organ transplantation remains the only definitive treatment, limited by donor scarcity and complications. This dissertation explores two strategies to generate transplantable cells. First, fumarylacetoacetate hydrolase (Fah)-null heterozygote pigs were created via AAV-DJ–mediated gene targeting and somatic cell nuclear transfer, enabling future human hepatocyte expansion. Second, mouse gallbladder cells were directly reprogrammed into beta-like cells using Neurog3, Pdx1, and MafA, with enhanced efficiency via retinoic acid and Notch inhibition. Transplanted cells engrafted long-term in diabetic mice. These approaches highlight promising avenues for cell-based therapies for liver disease and diabetes.