Human chemically derived hepatic progenitors (hCdHs) reprogrammed using three chemicals—HGF, A83-01, and CHIR99021 (collectively denoted as “HAC”)—have been suggested as a novel therapeutic for patients with severe liver diseases in our previous study. Despite its high proliferation and re-differentiation ability into functional hepatocytes, the reprogramming mechanism of hCdHs remained unknown. Recently, it has been reported that autophagy, a self-degradation process, is responsible for stem cell metabolism. In this study, we investigated whether autophagy regulates the generation mechanism of CdHs, mainly using hepatocytes from C57BL/6 mice, with additional analysis using human hepatocytes. As a result, we found that autophagy flux is inhibited during the generation of mouse CdHs (mCdHs) by A83-01, which is compensated by CHIR99021. Moreover, the suppression of autophagy by bafilomycin A1 enhanced the proliferation ability of mCdHs during the generation process. hCdHs also showed a similar autophagy inhibition pattern to mCdHs during the generation process. Taken together, our study indicates that autophagy is downregulated during the generation of CdHs, promoting their proliferation. This may contribute to the production of hCdHs with stable productivity, which may serve as a therapeutic for severe liver diseases.

Extracellular vesicles (EVs) are crucial mediators of intercellular communication, which facilitate the transfer of bioactive molecules such as proteins, lipids, and nucleic acids. Their high biocompatibility and intrinsic targeting abilities make them promising candidates for therapeutics, drug delivery, and disease biomarkers. In liver diseases, EVs are essential in liver regeneration, fibrosis modulation, and ischemia-reperfusion injury repair, and EV-derived biomarkers have shown potential for non-invasive disease monitoring, particularly in hepatitis B virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. This review provides a comprehensive overview of EV biology, cellular sources, isolation techniques, and strategies to enhance their therapeutic potential. Furthermore, we discuss the role of EVs in liver regeneration and their clinical application in biomarker discovery. Despite significant advancements in EV-based therapies, challenges such as scalability, standardization, immunogenicity, and regulatory approval remain key hurdles for clinical translation. Future research should focus on optimizing EV bioengineering, refining isolation methods, and addressing regulatory concerns to facilitate successful application of EVs in liver disease management and precision medicine.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.

The progress of transplantation has been propelled forward by animal experiments.Animal models have not only provided opportunities to understand complex immune mechanisms in transplantation but also served as a platform to assess therapeutic interventions. While small animals have been instrumental in uncovering new therapeutic concepts related to immunosuppression and immune tolerance, the progression to human trials has largely been driven by studies in large animals. Recent research has begun to explore the potential of porcine organs to address the shortage of available organs. The consistent progress in transplant immunology research can be attributed to a thorough understanding of animal models. This review provides a comprehensive overview of the available animal models, detailing their modifications, strengths, and weaknesses, as well as their historical applications, to aid researchers in selecting the most suitable model for their specific research needs.