Human iPSC-liver organoid transplantation reduces fibrosis through immunomodulation.

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver-like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure.

Development of the nervous system in mouse liver.

Background: The role of the hepatic nervous system in liver development remains unclear. We previously created functional human micro-hepatic tissue in mice by co-culturing human hepatic endodermal cells with endothelial and mesenchymal cells. However, they lacked Glisson's sheath [the portal tract (PT)].

Evaluation of immunosuppression protocols for MHC-matched allogeneic iPS cell-based transplantation using a mouse skin transplantation model.

Background: Off-the-shelf major histocompatibility complex (MHC)-matched iPS cells (iPSC) can potentially initiate host immune responses because of the existence of numerous minor antigens. To suppress allo-immune responses, combination of immunosuppressants is usually used, but its efficacy to the allogeneic iPSC-based transplantation has not been precisely evaluated.

Methods: Three transplantation models were used in this study; MHC-matched, minor antigen-mismatched mouse skin or iPSC-graft transplantation, and fully allogeneic human iPSC-derived liver organoid transplantation in immune-humanized mice.

Serous Membrane Detachment with Ultrasonic Homogenizer Improves Engraftment of Fetal Liver to Liver Surface in a Rat Model of Cirrhosis.

Liver transplantation is the most effective treatment for end-stage cirrhosis. However, due to serious donor shortages, new treatments to replace liver transplantation are sorely needed. Recent studies have focused on novel therapeutic methods using hepatocytes and induced pluripotent stem cells, we try hard to develop methods for transplanting these cells to the liver surface.

A Novel Orthotopic Liver Cancer Model for Creating a Human-like Tumor Microenvironment.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. This study aims to develop a new method to generate an HCC mouse model with a human tumor, and imitates the tumor microenvironment (TME) of clinical patients. Here, we have generated functional, three-dimensional sheet-like human HCC organoids in vitro, using luciferase-expressing Huh7 cells, human iPSC-derived endothelial cells (iPSC-EC), and human iPSC-derived mesenchymal cells (iPSC-MC).

Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models.

Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice.

Development of a Method for Scaffold-Free Elastic Cartilage Creation.

Microtia is a congenital aplasia of the auricular cartilage. Conventionally, autologous costal cartilage grafts are collected and shaped for transplantation. However, in this method, excessive invasion occurs due to limitations in the costal cartilage collection.

Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model.

Transplantation of liver organoids has been investigated as a treatment alternative to liver transplantation for chronic liver disease. Transportal approach can be considered as a method of delivering organoids to the liver. It is important to set the allowable organoid amount and verify translocation by intraportal transplantation.

Transplantation of fetal liver tissue coated by ultra-purified alginate gel over liver improves hepatic function in the cirrhosis rat model.

In this study, we used a new coating agent, that is, ultra-purified alginate gel (UPAL), for fetal liver tissue transplantation. This study aims to compare the effect of UPAL with the effect of other coating agents on improving the effect of fetal liver tissue transplantation in a liver cirrhosis rat model. Prior to the transplantation of wild-type ED14 fetal liver tissues, various coating agents were separately applied on the liver surface of rats with cirrhosis.

Novel liver fibrosis model in Macaca fascicularis induced by thioacetamide.

Although transplantation is the only definitive treatment for liver cirrhosis, there remains a shortage of donors, necessitating that novel treatments be developed. We aimed to establish a liver fibrosis model in Macaca fascicularis that can help accelerate preclinical research. Liver fibrosis was induced by administering thioacetamide (TAA) and carbon tetrachloride (CCl).

The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats.

In this study, we reveal that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage. The liver organoids significantly reconstituted the hepatocytes; hence, the liver was significantly enlarged in this group, compared to the monolayer cell transplantation group in the retrorsine/partial hepatectomy (RS/PH) model. In the liver organoid transplantation group, the bile ducts were located in the donor area and connected to the recipient bile ducts.

Recapitulation of hepatitis B virus-host interactions in liver organoids from human induced pluripotent stem cells.

Therapies against hepatitis B virus (HBV) have improved in recent decades; however, the development of individualized treatments has been limited by the lack of individualized infection models. In this study, we used human induced pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that inherited the genetic background of the donor, and evaluated its application in modeling HBV infection and exploring virus-host interactions. To establish a functional hiPSC-LO, we cultured hiPSC-derived endodermal, mesenchymal, and endothelial cells with a chemically defined medium in a three-dimensional microwell culture system.

Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness.

Purpose: Aldehyde dehydrogenase1 (ALDH1) is widely accepted as a stem cell marker for normal breast as well as in breast cancer. Although the clinical impact of ALDH1 was observed in our previous study, we do not know how ALDH1 affects stem cell features resulting in worsening of prognosis in breast cancer. The purpose of this study is to explore ALDH1-related gene and its function on cancer stem cell (CSC).

Antisense RNA transcripts in the blood may be novel diagnostic markers for colorectal cancer.

Numerous genetic studies have been conducted regarding the occurrence of colorectal cancer (CRC) and the prognosis using microarrays. However, adequate investigations into the diagnostic application of microarrays have yet to be performed. The simplicity and accuracy of diagnosis and prognosis tracking are important requirements for its processes, and the use of blood cells for diagnosis is considered to be suitable to meet these requirements.

Terpinen-4-ol inhibits colorectal cancer growth via reactive oxygen species.

Terpinen-4-ol (TP4O) is the main component of the essential oil extracted from , known as the tea tree, of the botanical family Myrtaceae. The anticancer effects of TP4O have been reported in several cancer cell lines. Previous reports have demonstrated that TP4O exerts anticancer effects by inducing apoptotic cell death in several cell lines; however, the underlying molecular mechanisms of these effects remain unclear.

Anticancer effect of linalool cancer-specific hydroxyl radical generation in human colon cancer.

Aim: To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.

Methods: The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosis-inducing effect of linalool was measured using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry with Annexin V.

Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease.

Liver cirrhosis is the end stage of chronic liver disease, but no definitive pharmacological treatment is currently available. It has been reported that thrombopoietin (TPO) promotes liver regeneration and improves liver cirrhosis by increasing platelet count. We have shown the direct effect of platelet transfusion on the improvement of liver function in patients with chronic liver disease.

New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury.

Aim: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid (HA) and sphingosine 1-phophate.

Methods: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate (S1P), and HA-S1P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion.

The Eltrombopag antitumor effect on hepatocellular carcinoma.

Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC.

1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.

Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice.

Sphingosine 1-phosphate has anti-apoptotic effect on liver sinusoidal endothelial cells and proliferative effect on hepatocytes in a paracrine manner in human.

Aim: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite released from erythrocytes and platelets, and is a potent stimulus for endothelial cell proliferation. However, the role of S1P on human liver sinusoidal endothelial cells (LSEC) remains unclear. The proliferation and inhibition of apoptosis in LSEC are involved in the promotion of liver regeneration and the suppression of liver injury after liver resection and transplantation.

Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage.

Although Kupffer cells (KCs) play an important role in the liver's immune response, their role in colon cancer metastasis to the liver is unclear. We here analyzed the relationship between KCs and tumor cells (TCs) in colon cancer metastasis to the liver. Fischer 344 (F344) rats were divided into control group (KC+ group) and KC elimination group (KC‑ group), in which KC elimination was induced by Cl2MDP liposome injection.

Signal transduction of platelet-induced liver regeneration and decrease of liver fibrosis.

Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration.

Interaction of kupffer cells and platelets determines the severity of ischemia-reperfusion injury in steatosis.

Liver steatosis increases the risk of postoperative complications following major liver resection, since the steatotic liver is susceptible to ischemia-reperfusion (IR) injury. However, it is unclear how IR injury changes in relation to the degree of hepatic steatosis. Previously, we reported that interaction between Kupffer cells (KCs) and platelets induced hepatic IR injury.

(-)-Epigallocatechin-3-gallate suppresses liver metastasis of human colorectal cancer.

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer.