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

2021 ◽  
Author(s):  
Yumi Kawakatsu-Hatada ◽  
Soichiro Murata ◽  
Akihiro Mori ◽  
Kodai Kimura ◽  
Hideki Taniguchi
Keyword(s):  
Liver Transplantation ◽  
Fetal Liver ◽  
Serous Membrane ◽  
Cavitron Ultrasonic Surgical Aspirator ◽  
Liver Surface ◽  
Induced Pluripotent ◽  
Liver Organoids ◽  
End Stage ◽  
New Treatments ◽  
Ultrasonic Homogenizer

Abstract 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. In the present study, we evaluated several methods for their efficiency in the detachment of serous membrane covering the liver surface for transplantation to the liver surface. The liver surface of dipeptidyl peptidase IV (DPPIV)-deficient rats in a cirrhosis model was detached by various methods, followed by fetal livers from DPPIV-positive rats were transplanted. We found that the engraftment rate and area as well as the liver function were improved in rats undergoing transplantation following serous membrane detachment with an ultrasonic homogenizer, which mimics Cavitron Ultrasonic Surgical Aspirator® (CUSA), compared with no detachment. Furthermore, the bleeding amount was lower with the ultrasonic homogenizer method than with the needle and electric scalpel methods. These findings provide evidence that transplantation to the liver surface with serous membrane detachment using CUSA might contribute to the development of new treatments for cirrhosis using liver organoids.

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

2021 ◽  
Vol 22 (21) ◽  
pp. 11589
Author(s):  
Yumi Kawakatsu-Hatada ◽  
Soichiro Murata ◽  
Akihiro Mori ◽  
Kodai Kimura ◽  
Hideki Taniguchi
Keyword(s):  
Liver Transplantation ◽  
Fetal Liver ◽  
Serous Membrane ◽  
Cavitron Ultrasonic Surgical Aspirator ◽  
Liver Surface ◽  
Induced Pluripotent ◽  
End Stage ◽  
New Treatments ◽  
Ultrasonic Surgical Aspirator ◽  
Ultrasonic Homogenizer

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. In the present study, we evaluated several methods for their efficiency in the detachment of serous membrane covering the liver surface for transplantation to the liver surface. The liver surface of dipeptidyl peptidase IV (DPPIV)-deficient rats in a cirrhosis model was detached by various methods, and then fetal livers from DPPIV-positive rats were transplanted. We found that the engraftment rate and area as well as the liver function were improved in rats undergoing transplantation following serous membrane detachment with an ultrasonic homogenizer, which mimics the Cavitron Ultrasonic Surgical Aspirator® (CUSA), compared with no detachment. Furthermore, the bleeding amount was lower with the ultrasonic homogenizer method than with the needle and electric scalpel methods. These findings provide evidence that transplantation to the liver surface with serous membrane detachment using CUSA might contribute to the development of new treatments for cirrhosis using cells or tissues.

In Vitro Hepatic Differentiation of Adult, Embryonic, Induced Pluripotent and Perinatal Stem-Cells

2020 ◽  
Keyword(s):  
Stem Cells ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Transplantation ◽  
Cell Transplantation ◽  
Hepatic Differentiation ◽  
End Stage Liver Disease ◽  
Induced Pluripotent ◽  
End Stage

Globally regenerative medicine is considered as one of the rapidly growing biomedical industry have objective to substitute damaged cells. Cell transplantation is less intrusive than whole-organ transplantation, and has been used to provide an alternative for patients to whole-organ transplantation. The End-stage liver disease comprises a subgroup of patients with cirrhosis who have signs of decompensation that is irreversible with medical treatment. The only restorative therapy for severe end-stage liver disease is orthotropic liver transplantation. However, liver transplantation has several limitations such as scarcity of organ donors, immunosuppressive drugs, and several postoperative complications. Thus, cell transplantation can be used for the treatment of end stage liver disorders to decrease the mortality in acute liver failure. Therefore, stem cells can be used for cellular therapy, development of liver disease models, and tissue-engineering applications. This review involved the studies conducted on the stem cells potential of hepatic differentiation, isolated from different sources. The PubMed and Google Scholar were searched for scientific studies reported the sources of stem cells based on their origin and their potential of hepatic differentiation in-vitro by using different tools of differentiation. All the research articles were selected in which solely hepatic differentiation in combination with different tools is reported. Keywords: Adult Stem Cells, Embryonic Stem Cells, Induced Pluripotent Stem Cells, In-vitro, Mesenchymal Stem Cells.

scholarly journals iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio055087
Author(s):  
Igor Gurevich ◽  
Sarah A. Burton ◽  
Christie Munn ◽  
Makiko Ohshima ◽  
Madelyn E. Goedland ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Drug Targets ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Alcoholic Fatty Liver ◽  
Induced Pluripotent ◽  
Liver Organoids ◽  
End Stage

ABSTRACTNon-alcoholic fatty liver disease (NAFLD) affects 30–40% of adults and 10% of children in the US. About 20% of people with NAFLD develop non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis and liver cancer, and is projected to be a leading cause of liver transplantation in the near future. Human induced pluripotent stem cells (iPSC) from NASH patients are useful for generating a large number of hepatocytes for NASH modeling applications and identification of potential drug targets. We developed a novel defined in vitro differentiation process to generate cryopreservable hepatocytes using an iPSC panel of NASH donors and apparently healthy normal (AHN) controls. iPSC-derived hepatocytes displayed stage specific phenotypic markers, hepatocyte morphology, with bile canaliculi. Importantly, both fresh and cryopreserved definitive endoderm and hepatoblasts successfully differentiated to pure and functional hepatocytes with increased CYP3A4 activity in response to rifampicin and lipid accumulation upon fatty acid (FA) treatment. End-stage hepatocytes integrated into three-dimensional (3D) liver organoids and demonstrated increased levels of albumin secretion compared to aggregates consisting of hepatocytes alone. End-stage hepatocytes derived from NASH donors demonstrated spontaneous lipidosis without FA supplementation, recapitulating a feature of NASH hepatocytes in vivo. Cryopreserved hepatocytes generated by this protocol across multiple donors will provide a critical cell source to facilitate the fundamental understanding of NAFLD/NASH biology and potential high throughput screening applications for preclinical evaluation of therapeutic targets.

scholarly journals Discontinuation of Passive Immunization Is Safe after Liver Transplantation for Combined HBV/HDV Infection

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 904
Author(s):  
Ramin Raul Ossami Saidy ◽  
Irina Sud ◽  
Franziska Eurich ◽  
Mustafa Aydin ◽  
Maximilian Paul Postel ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Overall Survival ◽  
Hepatitis B ◽  
Graft Function ◽  
Passive Immunization ◽  
Standard Regimen ◽  
Long Term Follow Up ◽  
Hdv Infection ◽  
End Stage

Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (p = 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear.

scholarly journals Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation

Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 1993
Author(s):  
Fernando Pérez-Sanz ◽  
Miriam Riquelme-Pérez ◽  
Enrique Martínez-Barba ◽  
Jesús de la Peña-Moral ◽  
Alejandro Salazar Nicolás ◽  
...  
Keyword(s):  
Machine Learning ◽  
Liver Transplantation ◽  
Learning Algorithms ◽  
Selection Procedure ◽  
Machine Learning Algorithms ◽  
Liver Biopsies ◽  
Convenient Technique ◽  
End Stage ◽  
Macrovesicular Steatosis

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

Low psoas muscle index as an unfavorable factor in children with end‐stage liver disease undergoing liver transplantation

2021 ◽  
Author(s):  
Settapong Jitwongwai ◽  
Chatmanee Lertudomphonwanit ◽  
Thitiporn Junhasavasdikul ◽  
Praman Fuangfa ◽  
Pornthep Tanpowpong ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Psoas Muscle ◽  
End Stage Liver Disease ◽  
End Stage

Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis

2021 ◽  
pp. 000313482110234
Author(s):  
Angela Sickels ◽  
Keyur B. Shah ◽  
Brianna Ruch ◽  
Adrian Cotterell ◽  
Inna Tchoukina ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Total Artificial Heart ◽  
Donor Pool ◽  
Cardiac Rejection ◽  
Recipient Age ◽  
Hospital Stays ◽  
The Mean ◽  
Domino Liver Transplantation ◽  
End Stage

Background Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients. Methods Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages. Results Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months. Discussion Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

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