ABSTRACT
Liver is involved in metabolic reactions, ammonia detoxification, and immunity. Multicellular liver tissue cultures are more desirable for drug screening, disease modeling, and researching transplantation therapy, than hepatocytes monocultures. Hepatocytes monocultures are not stable for long. Further, hepatocyte-like cells induced from pluripotent stem cells and in vivo hepatocytes are functionally dissimilar. Organoid technology circumvents these issues by generating functional ex vivo liver tissue from intrinsic liver progenitor cells and extrinsic stem cells, including pluripotent stem cells. To function as in vivo liver tissue, the liver organoid cells must be arranged precisely in the 3-dimensional space, closely mimicking in vivo liver tissue. Moreover, for long term functioning, liver organoids must be appropriately vascularized and in contact with neighboring epithelial tissues (e.g., bile canaliculi and intrahepatic bile duct, or intrahepatic and extrahepatic bile ducts). Recent discoveries in liver developmental biology allows one to successfully induce liver component cells and generate organoids. Thus, here, in this review, we summarize the current state of knowledge on liver development with a focus on its application in generating different liver organoids. We also cover the future prospects in creating (functionally and structurally) in vivo-like liver organoids using the current knowledge on liver development.
ABSTRACT
Hepatocytes are liver parenchymal cells involved in performing various metabolic reactions. During the development of therapeutic drugs, toxicological assays are conducted using hepatocyte cultures before clinical trials. However, since primary hepatocytes cannot proliferate and rapidly lose their functions in vitro, many efforts have been put into modifying culture conditions to expand primary hepatocytes and induce hepatocyte functions in intrinsic and extrinsic stem/progenitor cells. In this chapter, we summarize recent advances in preparing hepatocyte cultures and induction of hepatocytes from various cellular sources.
Subject(s)
Hepatocytes , Stem Cells , Hepatocytes/metabolism , HumansABSTRACT
BACKGROUND: 18F-FDG-PET is defined as a biomarker of neuronal injury according to the revised National Institute on AgingAlzheimer's Association criteria. OBJECTIVE: The objective of this multicenter prospective cohort study was to examine the value of 18F-FDG-PET in predicting the development of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS: In total, 114 patients with MCI at 9 participating institutions underwent clinical and neuropsychological examinations, MRI, and 18F-FDG-PET at baseline. The cases were visually classified into predefined dementia patterns by three experts. Anautomated analysis for 18F-FDG-PET was also performed to calculate the PET score. Subjects were followed periodically for 3 years, and progression to dementia was evaluated. RESULTS: In 47% of the patients with MCI, progression of symptoms justified the clinical diagnosis of "probable AD". The PET visual interpretation predicted conversion to AD during 3-year follow-up with an overall diagnostic accuracy of 68%. Overall diagnostic accuracy of the PET score was better than that of PET visual interpretation at all follow-up intervals, and the optimized PET score threshold revealed the best performance at the 2-year follow-up interval with an overall diagnostic accuracy of 83%,a sensitivity of 70%, and a specificity of 90%. Multivariate logistic regression analysis identified the PET score as the most significant predictive factor distinguishing AD converters from non-converters. CONCLUSION: The PET score is the most statistically significant predictive factor for conversion from MCI to AD, and the diagnostic performance of the PET score is more promising for rapid converters over 2 years.
