Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation

AbstractPurpose of ReviewWe will review the recent developments of cell sheet technology as a feasible tissue engineering approach. Specifically, we will focus on the technological advancement for engineering functional liver tissue using cell sheet technology, and the associated therapeutic effect of cell sheets for liver diseases, highlighting hemophilia.Recent FindingsCell-based therapies using hepatocytes have recently been explored as a new therapeutic modality for patients with many forms of liver disease. We have developed a cell sheet technology, which allows cells to be harvested in a monolithic layer format. We have succeeded in fabricating functional liver tissues in mice by stacking the cell sheets composed of primary hepatocytes. As a curative measure for hemophilia, we have also succeeded in treating hemophilia mice by transplanting of cells sheets composed of genetically modified autologous cells.SummaryTissue engineering using cell sheet technology provides the opportunity to create new therapeutic options for patients with various types of liver diseases.
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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Semin Thromb Hemost DOI: 10.1055/s-0039-1688445Hemophilia is a monogenic disease with robust clinicolaboratory correlations of severity. These attributes coupled with the availability of experimental animal models have made it an attractive model for gene therapy. The road from animal models to human clinical studies has heralded significant successes, but major issues concerning a previous immunity against adeno-associated virus and transgene optimization remain to be fully resolved. Despite significant advances in gene therapy application, many questions remain pertaining to its use in specific populations such as those ...
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
Conclusions: Data show that the rate of TEs within licensed indications is low (0.17%), as was originally described in the US PI from 1999-2009. It has remained stable over time during postapproval surveillance in multiple US and global registries, with active surveillance for safety information across the 4 approved indications. In postmarketing safety report assessments of patients with CHwI receiving concomitant treatment with aPCCs, older patients, particularly those with AH who are receiving other hemostatic agents, and patients with a history of cardiac and vascular disease may have an increased risk of developing TE...
Source: Blood - Category: Hematology Authors: Tags: 322. Disorders of Coagulation or Fibrinolysis: Poster I Source Type: research
Hemophilia B (HB) is a prime model for gene therapy. While data from current clinical trials using AAV-mediated liver-targeted FIX gene therapy are very encouraging, this protocol can only be applied to adults without liver disease or anti-AAV antibodies. Thus, developing another gene therapy protocol is desired. Our previous studies have demonstrated that platelet-targeted FIX expression driven by the platelet-specific αIIb promoter (2bF9) restores hemostasis and induces immune tolerance in HB mice (Chen et al. Mol Ther 2014). To improve the efficacy, we used a codon-optimized hyperfunctional FIX Padua (2bCoF9R338L)...
Source: Blood - Category: Hematology Authors: Tags: 321. Blood Coagulation and Fibrinolytic Factors: Animal Models and Therapeutic Targets in Thrombosis and Hemostasis Source Type: research
This study aimed to assess the associations between CLD and its risk factors using data from the H3 study, and to suggest implications for optimal care. Data from 13 European countries were collected at a single time-point (2011–2013). Univariate and multivariate logistic regression (MLR) analyses were performed. A total of 532 PWH were included with either hemophilia A (n = 467) or hemophilia B (n = 65). A total of 127 (24%) were diagnosed with CLD. Hepatitis C virus (HCV), human immunodeficiency virus (HIV), total cholesterol, and severe hemophilia were significant risk factors in univariate logistic regr...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Conclusions Cell transplantation devices that assist the anastomosis of grafts with the host can be potentially used as a minimally invasive ectopic liver accessory to augment liver-specific functions as well as potentially treat various pathologies associated with compromised functions of liver, such as hemophilia B or alpha-1 antitrypsin deficiency.
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science—Liver Source Type: research
Semin Liver Dis 2018; 38: 112-120 DOI: 10.1055/s-0038-1655774Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion. PMID: 2968156...
Source: Drug Discoveries and Therapeutics - Category: Drugs & Pharmacology Tags: Drug Discov Ther Source Type: research
In this study, we attempted to show the effectiveness of human iPS cell-based liver-like tissue engineering at an extrahepatic site for treatment of hemophilia B, also called factor IX (FIX) deficiency. HLCs were transplanted under the kidney capsule where the transplanted cells could be efficiently engrafted. Ten weeks after the transplantation, human albumin (253 μg/mL) and α-1 antitrypsin (1.2 μg/mL) could be detected in the serum of transplanted mice. HLCs were transplanted under the kidney capsule of FIX-deficient mice. The clotting activities in the transplanted mice were approximately 5% of those in wild...
Source: Cell Transplantation - Category: Cytology Authors: Tags: Cell Transplant Source Type: research
Conclusion: These results suggest the potential use of ADHLSCs in the treatment of hemophilia A.
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science-Liver Source Type: research
ConclusionAfter 30 years of infection, 40% of the patients who had evidence of chronic HCV had developed advanced liver disease, such as cirrhosis and HCC, or had died from liver‐related causes. This proportion is high relative to similar international cohorts despite good anti‐HCV treatment uptake and responses.
Source: Haemophilia - Category: Hematology Authors: Tags: ORIGINAL ARTICLE Source Type: research
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