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Background: The process of liver organogenesis has served as a paradigm for organ formation. However, there remains a lack of understanding regarding early mouse and human liver bud morphogenesis and early liver volumetric growth. Elucidating dynamic changes in liver volumes is critical for understanding organ development, implementing toxicological studies, and for modeling hPSC‐derived liver organoid growth. New visualization, analysis, and experimental techniques are desperately needed. Results: Here, we combine observational data with digital resources, new 3D imaging approaches, retrospective analysis of liver volume data, mathematical modeling, and experiments with hPSC‐derived liver organoids. Mouse and human liver organogenesis, characterized by exponential growth, demonstrate distinct spatial features and growth curves over time, which we mathematically modeled using Gompertz models. Visualization of liver‐epithelial and septum transversum mesenchyme (STM) interactions suggests extended interactions, which together with new spatial features may be responsible for extensive exponential growth. These STM interactions are modeled with a novel in vitro human pluripotent stem cell (hPSC)‐derived hepatic organoid system that exhibits cell migration. Conclusions: Our methods enhance our understanding of liver organogenesis, with new 3D visualization, analysis, mathematical modeling, and in vitro models with hPSCs. Our approach highlights mouse and human differences and provides potential hypothesis for further investigation in vitro and in vivo. Key Findings: We developed a new approach that enables quantitative visualization and analysis of mouse and human early liver growth by using available online databases.We identify potentially new spatial features of liver bud growth, and establish the importance of liver‐STM interactions with both imaging/analysis and a novel assay for liver bud migration.Our studies provide a visual and quantitative comparison of liver bud growth. These studies improve our understanding of mouse and human liver organogenesis [ABSTRACT FROM AUTHOR]

The field of organoid engineering promises to revolutionize medicine with wide‐ranging applications of scientific, engineering, and clinical interest, including precision and personalized medicine, gene editing, drug development, disease modelling, cellular therapy, and human development. Organoids are a three‐dimensional (3D) miniature representation of a target organ, are initiated with stem/progenitor cells, and are extremely promising tools with which to model organ function. The biological basis for organoids is that they foster stem cell self‐renewal, differentiation, and self‐organization, recapitulating 3D tissue structure or function better than two‐dimensional (2D) systems. In this review, we first discuss the importance of epithelial organs and the general properties of epithelial cells to provide a context and rationale for organoids of the liver, pancreas, and gall bladder. Next, we develop a general framework to understand self‐organization, tissue hierarchy, and organoid cultivation. For each of these areas, we provide a historical context, and review a wide range of both biological and mathematical perspectives that enhance understanding of organoids. Next, we review existing techniques and progress in hepatobiliary and pancreatic organoid engineering. To do this, we review organoids from primary tissues, cell lines, and stem cells, and introduce engineering studies when applicable. We discuss non‐invasive assessment of organoids, which can reveal the underlying biological mechanisms and enable improved assays for growth, metabolism, and function. Applications of organoids in cell therapy are also discussed. Taken together, we establish a broad scientific foundation for organoids and provide an in‐depth review of hepatic, biliary and pancreatic organoids. [ABSTRACT FROM AUTHOR]

The reshaping of the world's aging population has created an urgent need for therapies for chronic diseases. Regenerative medicine offers a ray of hope, and its complex solutions include material, cellular, or tissue systems. We review basics of regenerative medicine/stem cells and describe how the field of molecular imaging, which is based on quantitative, noninvasive, imaging of biological events in living subjects, can be applied to regenerative medicine in order to interrogate tissues in innovative, informative, and personalized ways. We consider aspects of regenerative medicine for which molecular imaging will benefit. Next, genetic and nanoparticle‐based cell imaging strategies are discussed in detail, with modalities like magnetic resonance imaging, optical imaging (near infra‐red, bioluminescence), raman microscopy, and photoacoustic microscopy), ultrasound, computed tomography, single‐photon computed tomography, and positron emission tomography. We conclude with a discussion of "next generation" molecular imaging strategies, including imaging host tissues prior to cell/tissue transplantation. [ABSTRACT FROM AUTHOR]

One of the major hurdles of cellular therapies for the treatment of liver failure is the low availability of functional human hepatocytes. While embryonic stem (ES) cells represent a potential cell source for therapy, current methods for differentiation result in mixed cell populations or low yields of the cells of interest. Here we describe a rapid, direct differentiation method that yields a homogeneous population of endoderm-like cells with 95% purity. Mouse ES cells cultured on top of collagen-sandwiched hepatocytes differentiated and proliferated into a uniform and homogeneous cell population of endoderm-like cells. The endoderm-like cell population was positive for Foxa2, Sox17, and AFP and could be further differentiated into hepatocyte-like cells, demonstrating hepatic morphology, functionality, and gene and protein expression. Incorporating the hepatocyte-like cells into a bioartificial liver device to treat fulminant hepatic failure improved animal survival, thereby underscoring the therapeutic potential of these cells. [ABSTRACT FROM AUTHOR]