BACKGROUNDTo solve the problem of liver transplantation donor insufficiency, an alternative cell transplantation therapy was investigated. We focused on amniotic epithelial cells (AECs) as a cell source because, unlike induced pluripotent stem cells, they are cost-effective and non-tumorigenic. The utilization of AECs in regenerative medicine, however, is in its infancy. A general profile for AECs has not been comprehensively analyzed. Moreover, no hepatic differentiation protocol for AECs has yet been established. To this end, we independently compiled human AEC libraries, purified amniotic stem cells (ASCs), and co-cultured them with mesenchymal stem cells (MSCs) and human umbilical vein endothelial cell (HUVECs) in a 3D system which induces functional hepatic organoids.AIMTo characterize AECs and generate functional hepatic organoids from ASCs and other somatic stem cellsMETHODSAECs, MSCs, and HUVECs were isolated from the placentae and umbilical cords of cesarean section patients. Amnion and primary AEC stemness characteristics and heterogeneity were analyzed by immunocytochemistry, Alkaline phosphatase (AP) staining, and flow cytometry. An adherent AEC subpopulation was selected and evaluated for ASC purification quality by a colony formation assay. AEC transcriptomes were compared with those for other hepatocytes cell sources by bioinformatics. The 2D and 3D culture were compared by relative gene expression using several differentiation protocols. ASCs, MSCs, and HUVECs were combined in a 3D co-culture system to generate hepatic organoids whose structure was compared with a 3D AEC sphere and whose function was elucidated by immunofluorescence imaging, periodic acid Schiff, and an indocyanine green (ICG) test.RESULTSAECs have certain stemness markers such as EPCAM, SSEA4, and E-cadherin. One AEC subpopulation was also either positive for AP staining or expressed the TRA-1-60 and TRA-1-81 stemness markers. Moreover, it could form colonies and its frequency was enhanced ten-fold in the adherent subpopulation after selective primary passage. Bioinformatics analysis of ribose nucleic acid sequencing revealed that the total AEC gene expression was distant from those of pluripotent stem cells and hepatocytes but some gene expression overlapped among these cells. TJP1, associated with epidermal growth factor receptor, and MET, associated with hepatocyte growth factor receptor, were upregulated and may be important for hepatic differentiation. In conventional flat culture, the cells turned unviable and did not readily differentiate into hepatocytes. In 3D culture, however, hepatic gene expression of the AEC sphere was elevated even under a two-step differentiation protocol. Furthermore, the organoids derived from the MSC and HUVEC co-culture showed 3D structure with polarity, hepatic-like glycogen storage, and ICG absorption/elimination.CONCLUSIONHuman amniotic epithelial cells are heterogeneous and certain subpopulations have high stemness. Under a 3D co-culture system, functional hepatic organoids were generated in...

BACKGROUND Hepatocellular carcinoma (HCC) accompanied by portal vein tumour thrombus (PVTT) presents an aggressive disease course, worsening liver function reserve, and a high recurrence rate. Clinical practice guidelines recommend systemic therapy as the first-line option for HCC with portal invasion. However, to achieve longer survival in these patients, the treatment strategy should be concluded with removal of the tumour by locoregional therapy. We experienced a case of initially unresectable HCC with main PVTT converted to radical hepatectomy after lenvatinib treatment. CASE SUMMARY A 59-year-old male with chronic hepatitis C infection visited our clinic as a regular post-surgery follow-up. Contrast-enhanced abdominal computed tomography revealed a liver mass diffusely located at the lateral segment with a massive PVTT extending from the umbilical portion to the main and contralateral third-order portal branches. With the diagnosis of unresectable HCC with Vp4 (main trunk/contralateral branch) PVTT, lenvatinib was started at 12 mg/d. The computed tomography taken 3 mo after starting lenvatinib showed regression of the PVTT, which had retreated to the contralateral first-order portal branch. He tolerated the full dose without major adverse effects. With cessation of lenvatinib for 7 d, radical left lobectomy and PVTT thrombectomy were conducted. The patient’s postoperative course was uneventful. Microscopically, the primary lesion showed fibrotic changes, with moderately to poorly differentiated tumour cells surrounded by granulation tissues in some areas. The majority of the PVTT showed necrosis. He was alive without recurrence for 8 mo. CONCLUSION This is the first case of HCC with Vp4 PVTT in which radical conversion hepatectomy was succeeded after lenvatinib treatment.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current treatments but lectin‐based therapy targeting cell surface glycans could be a promising new horizon. Here, we report a novel lectin‐based phototherapy (Lec‐PT) that combines the PDAC targeting ability of rBC2LCN lectin to a photoabsorber, IRDye700DX (rBC2‐IR700), resulting in a novel and highly specific near‐infrared, light‐activated, anti‐PDAC therapy. Lec‐PT cytotoxicity was first verified in vitro with a human PDAC cell line, Capan‐1, indicating that rBC2‐IR700 is only cytotoxic upon cellular binding and exposure to near‐infrared light. The therapeutic efficacy of Lec‐PT was subsequently verified in vivo using cell lines and patient‐derived, subcutaneous xenografting into nude mice. Significant accumulation of rBC2‐IR700 occurs as early as 2 hours postintravenous administration while cytotoxicity is only achieved upon exposure to near‐infrared light. Repeated treatments further slowed tumor growth. Lec‐PT was also assessed for off‐target toxicity in the orthotopic xenograft model. Shielding of intraperitoneal organs from near‐infrared light minimized off‐target toxicity. Using readily available components, Lec‐PT specifically targeted pancreatic cancer with high reproducibility and on‐target, inducible toxicity. Rapid clinical development of this method is promising as a new modality for treatment of pancreatic cancer.

Background: This study investigated the effectiveness of using patient participation goal attainment scaling in a telenursing system for self-management behavior in two Japanese type 2 diabetic patients. Methods: The intervention consisted of using goal attainment scaling to set goals, and efforts toward realizing these goals were made using a telenursing system that included on-demand webcam conversations, e-mail and phone calls. Over the intervention period of 6 months, the patients performed daily self-monitoring and the nurse provided telenursing support according to the patients' needs and nursing care requirements. Results: Both patients had improved self-management behavior and a positive opinion of the telenursing system and goal attainment scaling. Conclusion: Incorporating goal attainment scaling into a telenursing system for type 2 diabetic patients was effective in continuing self-management behavior, suggesting that it is effective in providing continued home nursing care in diabetic patients.

Background As a critical cellular component in the hepatic stem cell niche, hepatic stellate cells (HSCs) play critical roles in regulating the expansion of hepatic stem cells, liver regeneration, and fibrogenesis. However, the signaling of HSCs, particularly that involved in promoting hepatic stem cell expansion, remains unclear. While the overexpression of galectins has been identified in regenerating liver tissues, their involvement in cell-cell interactions between HSCs and hepatic stem cells remains to be elucidated. Methods To generate a liver regeneration rat model and establish a hepatic oval cell microenvironment as a stem cell niche, 2-acetylaminofluorene treatment plus partial hepatectomy was performed. Immunofluorescence staining was conducted to detect the emergence of hepatic stem cells and their niche. Liver parenchymal cells, non-parenchymal cells, and HSCs were isolated for gene and protein expression analysis by qPCR or western blotting. To evaluate the effect of galectins on the colony-forming efficiency of hepatic stem cells, c-Kit−CD29+CD49f+/lowCD45−Ter-119− cells were cultured with recombinant galectin protein, galectin antibody, galectin-producing HSCs, and galectin-knockdown HSCs. Results Following liver injury, the cytokeratin 19+ ductal cells were robustly induced together with the emergence of OV6+CD44+CD133+EpCAM+ hepatic stem cells. The activated desmin+ HSCs were recruited around the periportal area and markedly enriched in the galectin-positive domain compared to the other non-parenchymal cells. Notably, the HSC fraction isolated from regenerating liver was accompanied by dramatically elevated gene and protein expression of galectins. Hepatic stem cells co-cultured with HSCs significantly enhanced colony-forming efficiency. Conversely, single or double knockdown of galectin-1 and galectin-3 led into a significant function loss, impaired the co-cultured hepatic stem cells to attenuated colony size, inhibited colony frequency, and reduced total cell numbers in colonies. On the other hand, the promotive function of galectins was further confirmed by recombinant galectin protein supplementation and galectins blocking antibodies. Conclusions Our findings, for the first time, demonstrated that galectins from activated HSCs contribute to hepatic stem cell expansion during liver regeneration, suggesting that galectins serve as important stem cell niche components.