scholarly journals Stem Cell-Based Therapies for Liver Diseases: State of the Art and New Perspectives

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Chiara Piscaglia ◽  
Mariachiara Campanale ◽  
Antonio Gasbarrini ◽  
Giovanni Gasbarrini
Keyword(s):  
Cell Biology ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Organ Shortage ◽  
Cell Therapies ◽  
Curative Therapy ◽  
Induced Pluripotent Cells ◽  
Liver Repopulation ◽  
Induced Pluripotent ◽  
End Stage

Millions of patients worldwide suffer from end-stage liver pathologies, whose only curative therapy is liver transplantation (OLT). Given the donor organ shortage, alternatives to OLT have been evaluated, including cell therapies. Hepatocyte transplantation has been attempted to cure metabolic liver disorders and end-stage liver diseases. The evaluation of its efficacy is complicated by the shortage of human hepatocytes and their difficult expansion and cryopreservation. Recent advances in cell biology have led to the concept of “regenerative medicine”, based on the therapeutic potential of stem cells (SCs). Different types of SCs are theoretically eligible for liver cell replacement. These include embryonic and fetal SCs, induced pluripotent cells, annex SCs, endogenous liver SCs, and extrahepatic adult SCs. Aim of this paper is to critically analyze the possible sources of SCs suitable for liver repopulation and the results of the clinical trials that have been published until now.

scholarly journals Cell-Based Regeneration and Treatment of Liver Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10276
Author(s):  
Julia Hofmann ◽  
Verena Hackl ◽  
Hannah Esser ◽  
Andras T. Meszaros ◽  
Margot Fodor ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Ex Vivo ◽  
Organ Shortage ◽  
Clinical Implementation ◽  
Organ Function ◽  
Novel Technologies ◽  
Recent Developments ◽  
Underlying Mechanisms ◽  
The Moment ◽  
End Stage

The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function.

scholarly journals The Role of B Cells in Adult and Paediatric Liver Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Arzoo M. Patel ◽  
Yuxin S. Liu ◽  
Scott P. Davies ◽  
Rachel M. Brown ◽  
Deirdre A. Kelly ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Liver Diseases ◽  
Cell Activation ◽  
Persistent Inflammation ◽  
Stage Disease ◽  
End Stage ◽  
The Impact

B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.

scholarly journals The First Two Liver Transplantations in Syria

2021 ◽  
pp. 296-304
Author(s):  
Fadi Rayya
Keyword(s):  
Arterial Thrombosis ◽  
Liver Diseases ◽  
Metabolic Disorders ◽  
Hepatic Cell ◽  
Routine Procedure ◽  
Curative Therapy ◽  
Vein Thrombosis ◽  
Liver Transplantations ◽  
End Stage

Liver transplantation (LT) is the only curative therapy for the end-stage liver diseases and some metabolic disorders which affect the hepatic cell like the Crigler-Najjar syndrome type 1 (CNSI). Although the LT is a routine procedure in many centers worldwide, the postoperative complications such as rejection, arterial thrombosis, and infection remain serious challenges even in big centers. In our paper, we demonstrate the first two LTs in Syria. The first one was performed on 6 February 2016 for an 11-year-old boy suffering from CNSI using an auxiliary LT, but unfortunately, he had a hepatic artery and portal vein thrombosis, so we removed the necrotic graft on the fifth postoperative day, and he survived. The second LT was for a 9-year-old boy, who had cryptogenic liver cirrhosis, and he lived for 31 days after the transplantation. In both transplants, grafts were obtained from living relative donors.

scholarly journals Diabetes Mellitus Is a Chronic Disease that Can Benefit from Therapy with Induced Pluripotent Stem Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8685
Author(s):  
Felipe Arroyave ◽  
Diana Montaño ◽  
Fernando Lizcano
Keyword(s):  
Diabetes Mellitus ◽  
Cell Biology ◽  
Diabetes Management ◽  
Therapeutic Option ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Induced Pluripotent Cells ◽  
New Findings ◽  
Induced Pluripotent ◽  
The Impact

Diabetes mellitus (DM) is one of the main causes of morbidity and mortality, with an increasing incidence worldwide. The impact of DM on public health in developing countries has triggered alarm due to the exaggerated costs of the treatment and monitoring of patients with this disease. Considerable efforts have been made to try to prevent the onset and reduce the complications of DM. However, because insulin-producing pancreatic β-cells progressively deteriorate, many people must receive insulin through subcutaneous injection. Additionally, current therapies do not have consistent results regarding the prevention of chronic complications. Leveraging the approval of real-time continuous glucose monitors and sophisticated algorithms that partially automate insulin infusion pumps has improved glycemic control, decreasing the burden of diabetes management. However, these advances are facing physiologic barriers. New findings in molecular and cellular biology have produced an extraordinary advancement in tissue development for the treatment of DM. Obtaining pancreatic β-cells from somatic cells is a great resource that currently exists for patients with DM. Although this therapeutic option has great prospects for patients, some challenges remain for this therapeutic plan to be used clinically. The purpose of this review is to describe the new techniques in cell biology and regenerative medicine as possible treatments for DM. In particular, this review highlights the origin of induced pluripotent cells (iPSCs) and how they have begun to emerge as a regenerative treatment that may mitigate the pathology of this disease.

scholarly journals Investigation of Thyroid Hormone Associated Gene-Regulatory Networks during Hepatogenesis using an Induced Pluripotent Stem Cell based Model

2021 ◽  
Author(s):  
Audrey Ncube ◽  
Nina Graffmann ◽  
Jan Greulich ◽  
Bo Scherer ◽  
Wasco Wruck ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Thyroid Hormone ◽  
Drug Screening ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Disease Modeling ◽  
Patient Specific ◽  
Number Of Patients ◽  
Induced Pluripotent ◽  
End Stage

Currently, the only treatment of end-stage liver diseases is liver transplantation. The worldwide shortage of donor organs and the high number of patients suffering from end-stage liver diseases, require alternative treatment approaches. Therefore, the generation of hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs) is a promising treatment option. HLCs are suitable for patient-specific drug screening, disease modeling and regenerative medicine. So far, they are immature and resemble the fetal state. In this study, we employed the combined thyroid hormones triiodo-L-thyronine (T3) and L-thyroxine (T4) to drive HLCs towards maturation. HLCs expressed the maturation markers ALBUMIN (ALB), ALPHA-1 ANTITRYPSIN (A1AT), CYTOCHROME P450 3A4 (CYP3A4) and TRANSTHYRETIN (TTR). Remarkably, stimulation with T3 and T4 slightly reduced the expression of the fetal marker CYTOCHROME P450 3A7 (CYP3A7) and had an even more pronounced effect on ALPHA-FETOPROTEIN (AFP) levels. Comparative transcriptome and associated pathways in unstimulated and T3 and T4 stimulated HLCs revealed regulated expression of numerous genes within for example the peroxisome proliferator-activated receptor (PPAR), transforming growth factor beta (TGF-β), mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) signaling pathways and thyroid hormone synthesis. We propose the inclusion of combined T3 andT4 in HLC differentiation protocols to enhance maturation and therefore provide additional improvement in their applications in drug screening and disease modeling.

scholarly journals Emerging Stem Cell Therapies: Treatment, Safety, and Biology

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Joel Sng ◽  
Thomas Lufkin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Autologous Transplantation ◽  
Building Blocks ◽  
Hematopoietic Stem ◽  
Cell Therapies ◽  
Adult T Cell Leukemia ◽  
Induced Pluripotent

Stem cells are the fundamental building blocks of life and contribute to the genesis and development of all higher organisms. The discovery of adult stem cells has led to an ongoing revolution of therapeutic and regenerative medicine and the proposal of novel therapies for previously terminal conditions. Hematopoietic stem cell transplantation was the first example of a successful stem cell therapy and is widely utilized for treating various diseases including adult T-cell leukemia-lymphoma and multiple myeloma. The autologous transplantation of mesenchymal stem cells is increasingly employed to catalyze the repair of mesenchymal tissue and others, including the lung and heart, and utilized in treating various conditions such as stroke, multiple sclerosis, and diabetes. There is also increasing interest in the therapeutic potential of other adult stem cells such as neural, mammary, intestinal, inner ear, and testicular stem cells. The discovery of induced pluripotent stem cells has led to an improved understanding of the underlying epigenetic keys of pluripotency and carcinogenesis. More in-depth studies of these epigenetic differences and the physiological changes that they effect will lead to the design of safer and more targeted therapies.

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Szczurek ◽  
M Gasior ◽  
M Skrzypek ◽  
G Kubiak ◽  
A Kuczaj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Coronary Sinus ◽  
Public Institution ◽  
Funding Source ◽  
Organ Shortage ◽  
Number Of Patients ◽  
End Stage ◽  
Medical University

Abstract   Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

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