000000736 001__ 736 000000736 005__ 20260120144838.0 000000736 0247_ $$2DOI$$a10.6083/M4H9936X 000000736 037__ $$aETD 000000736 245__ $$aNovel cell therapies for liver disease and type 1 diabetes 000000736 260__ $$bOregon Health and Science University 000000736 269__ $$a2012 000000736 336__ $$aDissertation 000000736 502__ $$bPh.D. 000000736 520__ $$aLiver disease and type 1 diabetes affect millions, yet whole-organ transplantation remains the only definitive treatment, limited by donor scarcity and complications. This dissertation explores two strategies to generate transplantable cells. First, fumarylacetoacetate hydrolase (Fah)-null heterozygote pigs were created via AAV-DJ–mediated gene targeting and somatic cell nuclear transfer, enabling future human hepatocyte expansion. Second, mouse gallbladder cells were directly reprogrammed into beta-like cells using Neurog3, Pdx1, and MafA, with enhanced efficiency via retinoic acid and Notch inhibition. Transplanted cells engrafted long-term in diabetic mice. These approaches highlight promising avenues for cell-based therapies for liver disease and diabetes. 000000736 540__ $$fCC BY 000000736 542__ $$fIn copyright - single owner 000000736 650__ $$aLiver Diseases$$021588 000000736 650__ $$aPancreas$$023506 000000736 650__ $$aLiver$$021580 000000736 650__ $$aPancreatic Diseases$$023509 000000736 650__ $$aTransplantation$$027278 000000736 650__ $$aDiabetes Mellitus, Type 1$$017673 000000736 650__ $$aCell- and Tissue-Based Therapy$$040537 000000736 650__ $$aCellular Reprogramming$$040575 000000736 6531_ $$acell nuclei 000000736 691__ $$aSchool of Medicine$$041369 000000736 692__ $$aDepartment of Molecular and Medical Genetics$$041428 000000736 7001_ $$aHickey, Raymond$$uOregon Health and Science University$$041354 000000736 7201_ $$aGrompe, Markus$$uOregon Health and Science University$$041354$$7Personal$$eMentor 000000736 8564_ $$9731de66f-06ff-4391-a142-f05b14d132c6$$s3365019$$uhttps://digitalcollections.ohsu.edu/record/736/files/739_etd.pdf$$ePublic$$23c940725f598413ebcb7bdbdecf71914$$31 000000736 905__ $$a/rest/prod/dr/26/xx/39/dr26xx39d 000000736 909CO $$ooai:digitalcollections.ohsu.edu:736$$pstudent-work 000000736 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000736 980__ $$aTheses and Dissertations