scholarly journals Liver and Hepatocyte Transplantation: What Can Pigs Contribute?

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaoxue Li ◽  
Ying Wang ◽  
Haiyuan Yang ◽  
Yifan Dai
Keyword(s):  
Clinical Application ◽  
Liver Diseases ◽  
Hepatocyte Transplantation ◽  
Major Surgery ◽  
Liver Support ◽  
Promising Alternative ◽  
Bridge To Transplant ◽  
Life Saving ◽  
Life Threatening ◽  
End Stage

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.

Rationale for the use of statins in liver disease

2017 ◽  
Vol 312 (5) ◽  
pp. G407-G412 ◽  
Author(s):  
Robert Schierwagen ◽  
Frank Erhard Uschner ◽  
Fernando Magdaleno ◽  
Sabine Klein ◽  
Jonel Trebicka
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Treatment Options ◽  
Statin Treatment ◽  
Chronic Liver ◽  
Special Focus ◽  
Chronic Liver Diseases ◽  
End Stage Liver Disease ◽  
Life Threatening ◽  
End Stage

The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.

scholarly journals Zebrafish as a New Tool in Heart Preservation Research

2021 ◽  
Vol 8 (4) ◽  
pp. 39
Author(s):  
Luciana Da Silveira Cavalcante ◽  
Shannon N. Tessier
Keyword(s):  
New Technologies ◽  
Ex Vivo ◽  
Machine Perfusion ◽  
Life Saving ◽  
First Choice ◽  
Heart Preservation ◽  
End Stage Heart Failure ◽  
Ischemia Tolerance ◽  
The 1960S ◽  
End Stage

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.

scholarly journals Preparedness for transplantation during COVID-19 outbreak: how to manage?

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
G Valdi ◽  
G Varadi ◽  
A Panzera ◽  
M Parpinel ◽  
R Peressutti
Keyword(s):  
Organ Transplantation ◽  
Task Force ◽  
Emergency Situation ◽  
Donor Pool ◽  
Surge Capacity ◽  
Emergency Procedures ◽  
Life Saving ◽  
Critical Patients ◽  
End Stage ◽  
Assessment Procedures

Abstract Problem When WHO declared COVID-19 “international”, it was important not to damage some critical patients who need emergency procedures like organ transplantation, due to end stage organ disease. In 2003 SARS outbreak demonstrated the vulnerability of organ transplantation services o network. Descritption If transplantation is required as a life-saving procedure, it can be conducted with appropriate risk infection assessment. It is crucial during these emergencies to assess donor pool, as it is expected to decrease. A crucial point is to organize and evaluate the surge capacity, in terms of understaffing and lack of supplies, especially in ICU. The research methods were literature review using Pub Med, CDC, ECDC, WHO, TTS, searching as key words “SARS-CoV-2”, “COVID-19”, “transplantation”, “preparedness”. The analysis has been conducted between Feb 26th 2020 and March 5th 2020. Results As happened during SARS breakout in 2003, it is essential to establish a task force for crisis, currently updated and skilled for this particular management. Preparedness should regard especially the adoption of donor safety assessment procedures, ICU capability, the availability of covid-19 test for all the donors, and the adoption of specific post-transplant care. It is essential in this case establish preparedness in several points: education and training of the staff, practice drills, inspection of supplies, evaluation of surge capacity, relocation of patients. Lessons SARS-CoV-2 imposed in public health to establish new protocols and guidelines, which should be regularly updated to be useful in other epidemics outbreaks or other emergency situation. These protocols should focus on donor pool and ICU capability in order to carry on transplantation activities. Key messages This outbreak has tested the resilience of the whole system by day-by-day updating for transplantation teams and preparedness of the staff involved in transplantation management. During outbreak, seems to be useful a task force for crisis in order to support organ transplantation services.

scholarly journals Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 289
Author(s):  
Adamasco Cupisti ◽  
Piergiorgio Bolasco ◽  
Claudia D’Alessandro ◽  
Domenico Giannese ◽  
Alice Sabatino ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Residual Renal Function ◽  
The Body ◽  
Uremic Toxins ◽  
End Stage Kidney Disease ◽  
Waste Products ◽  
Hemodialysis Treatment ◽  
Life Saving ◽  
Kidney Replacement Therapy ◽  
End Stage

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

scholarly journals Ifosfamide May Be Safely Used in Patients with End Stage Renal Disease on Hemodialysis

Sarcoma ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Sheron Latcha ◽  
Robert G. Maki ◽  
Gary K. Schwartz ◽  
Carlos D. Flombaum
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Response To Therapy ◽  
Common Side Effect ◽  
Pharmacokinetic Data ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage ◽  
Metastatic Sarcoma ◽  
Radiographic Improvement

Background. Pharmacokinetic data on clearance of ifosfamide in hemodialysis patients are limited. Consequently, these patients are excluded from therapy with this agent. We review the outcomes for patients at our institution with end stage renal disease on dialysis who received ifosfamide for metastatic sarcoma.Patients and Methods. We treated three patients with end stage renal disease on hemodialysis with escalating doses of ifosfamide. Data on radiographic response to therapy, WBC and platelet counts, signs or symptoms of infection, neuropathy and bladder toxicity are reported. Starting doses of ifosfamide were based on review of the literature available with subsequent modifications based on each patient's prior exposure to myelosuppressive agents and on symptoms of neurotoxicity and the degree of myelosuppression following each cycle of chemotherapy.Results. Myelosuppression was the most common side effect from therapy, but no patient developed a life threatening infection, neurotoxicity, or hematuria. One patient developed epistaxis in the setting of thrombocytopenia while on warfarin therapy. All patients had clinical evidence for therapeutic response and two had documented radiographic improvement following ifosfamide administration.Conclusion. Ifosfamide can be used safely in combination with hemodialysis in patients with end stage renal disease.

scholarly journals Pretransplant Prediction of Posttransplant Survival for Liver Recipients with Benign End-Stage Liver Diseases: A Nonlinear Model

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e31256 ◽  
Author(s):  
Ming Zhang ◽  
Fei Yin ◽  
Bo Chen ◽  
You Ping Li ◽  
Lu Nan Yan ◽  
...  
Keyword(s):  
Nonlinear Model ◽  
Liver Diseases ◽  
End Stage

scholarly journals Myelodysplastic Syndrome Clinically Presenting with the “Classic TTP Pentad”

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Santiago Fabián Moscoso Martínez ◽  
Evelyn Carolina Polanco Jácome ◽  
Elizabeth Guevara ◽  
Vijay Mattoo
Keyword(s):  
Myelodysplastic Syndrome ◽  
Clinical Presentation ◽  
Renal Involvement ◽  
Medical Emergency ◽  
Complete Blood Cell Count ◽  
Blood Cell Count ◽  
Thrombocytopenic Purpura ◽  
Life Saving ◽  
Threatening Condition ◽  
Life Threatening

The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP “pentad” of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case.

scholarly journals Innovative Biotechnology for Generation of Cardiac Tissue

2021 ◽  
Vol 11 (12) ◽  
pp. 5603
Author(s):  
Greta Ionela Barbulescu ◽  
Florina Maria Bojin ◽  
Valentin Laurentiu Ordodi ◽  
Iacob Daniel Goje ◽  
Taddeus Paul Buica ◽  
...  
Keyword(s):  
Stem Cells ◽  
Electric Field ◽  
Cardiac Tissue ◽  
Sodium Dodecyl ◽  
Human Mesenchymal Stem Cells ◽  
Coronary Perfusion ◽  
Decellularized Extracellular Matrix ◽  
Life Saving ◽  
Cellular Debris ◽  
End Stage

Heart transplantation remains the only curative treatment for end-stage heart failure. This life-saving option continues to be limited by the low number of organ donors, graft rejection and adverse effects of immunosuppressants. Engineering bioartificial hearts from acellular native-derived scaffolds and stem cells has gained attention because of its potential to overcome these limitations. In this study, rat hearts (n = 20) were decellularized by means of coronary perfusion with 1% sodium dodecyl sulfate (SDS) in a modified Langendorff device. The electrical field behavior of the SDS molecule was studied and it was assumed that when applying an alternating current, the exposure time of the tissue to the detergent might decrease. To repopulate the decellularized extracellular matrix (ECM), human mesenchymal stem cells (hMSCs) were used, induced to differentiate into cardiomyocytes (CMs) with 5-azacytidine (5-aza). The results showed no cellular debris and an intact ECM following decellularization. Decellularization in the presence of an electric field proved to be faster, decreasing the potential risk of ECM damage due to the detergent. After cell seeding and culturing of eight scaffolds with hMSCs, the recellularization process was analyzed using optic microscopy (OM), which showed cells suggestive for CMs. This study presents a novel and efficient decellularization protocol using an electric field and suggests that hMSCs can be useful in the generation of a bioartificial heart.

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