Generation of in vivo-like multicellular liver organoids by mimicking developmental processes: A review.

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.

Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by the tumor microenvironment (TME). In this study, to recapitulate the PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in an air-liquid interface. FPCOs were further induced to resemble two distinct aspects of PDAC tissue. Quiescent FPCOs were drug resistant, likely because the TME consisted of abundant extracellular matrix proteins that were secreted from the various types of cancer-associated fibroblasts (CAFs) derived from hiPSCs. Proliferative FPCOs could re-proliferate after anticancer drug treatment, suggesting that this type of FPCO would be useful for studying PDAC recurrence. Thus, we generated PDAC organoids that recapitulate the heterogeneity of PDAC tissue and are a potential platform for screening anticancer drugs.

Organ Donation after Extracorporeal Cardiopulmonary Resuscitation and Brain Death.

A 38-year-old primipara Japanese woman suffered cardiac arrest due to a pulmonary thromboembolism 1 day after undergoing a cesarean section. Extracorporeal cardiopulmonary resuscitation was initiated and extracorporeal membrane oxygenation support was needed for 24 h. Despite intensive care, the patient was diagnosed with brain death on day 6. With the family's consent, comprehensive end-of-life care including organ donation was discussed based on our hospital's policy. The family decided to donate her organs. Specific training and education are required for emergency physicians to optimize the process of incorporating organ donation into end-of-life care while respecting the patient's and family's wishes.

Right Hemiplegia Following Acute Carbon Monoxide Poisoning.

Acute carbon monoxide (CO) poisoning remains a common cause of poison-related death and influences neurological function. An 83-year-old female was transferred to our emergency unit due to hypertension with dizziness, headache, and right hemiplegia. There was no radiographic evidence of ischemic stroke. The family members reported that the patient may have been exposed to CO by briquettes burned inside a closed room. High flow oxygen therapy was given for suspected CO intoxication and her symptoms quickly improved. Although we do not have clear evidence, we presume that hemiplegia in our patient was caused by CO intoxication, based on rapid recovery with oxygen therapy, carboxyhemoglobin (COHb) level elevation (3.0%), polycythemia, and neuroimaging. Despite the hematogenous effects of CO, paralysis appeared to be more severe on her right side than on her left side. MRI and blood tests helped to support CO as the suspected cause of her hemiplegia. This case reconfirms the importance of medical interviewing by medical practitioners, even in an emergency setting.

Real-time processing for full-range Fourier-domain optical-coherence tomography with zero-filling interpolation using multiple graphic processing units.

The real-time display of full-range, 2048?axial pixelx1024?lateral pixel, Fourier-domain optical-coherence tomography (FD-OCT) images is demonstrated. The required speed was achieved by using dual graphic processing units (GPUs) with many stream processors to realize highly parallel processing. We used a zero-filling technique, including a forward Fourier transform, a zero padding to increase the axial data-array size to 8192, an inverse-Fourier transform back to the spectral domain, a linear interpolation from wavelength to wavenumber, a lateral Hilbert transform to obtain the complex spectrum, a Fourier transform to obtain the axial profiles, and a log scaling. The data-transfer time of the frame grabber was 15.73?ms, and the processing time, which includes the data transfer between the GPU memory and the host computer, was 14.75?ms, for a total time shorter than the 36.70?ms frame-interval time using a line-scan CCD camera operated at 27.9?kHz. That is, our OCT system achieved a processed-image display rate of 27.23 frames/s.