scholarly journals Functional Assessment of the Quality of Human Hepatocyte Preparations for Cell Transplantation

2008 ◽  
Vol 17 (10-11) ◽  
pp. 1211-1219 ◽  
Author(s):  
María Teresa Donato ◽  
Agustín Lahoz ◽  
Sandra Montero ◽  
Ana Bonora ◽  
Eugenia Pareja ◽  
...  

Hepatocyte transplantation is an alternative therapy to orthotopic liver transplantation for the treatment of liver diseases. Good quality freshly isolated or cryopreserved human hepatocytes are needed for clinical transplantation. However, isolation, cryopreservation, and thawing processes can seriously impair hepatocyte viability and functionality. The aim of the present study was to develop a fast and sensitive procedure to estimate the quality of hepatocyte preparations prior to clinical cell infusion. To this end, cell viability, attachment efficiency, and metabolic competence (urea synthesis and drug-metabolizing P450 activities) were selected as objective criteria. Viability of hepatocyte suspension was estimated by trypan blue staining. DNA content of attached cells 50 min after hepatocyte platting to fibronectin/collagen-coated dishes was quantified to estimate adherence capacity. Urea production was determined after incubating hepatocyte suspensions with 2 mM ClNH4 for 30 min. The cytochrome P450 function was assayed by a 30-min incubation of hepatocyte suspension with a cocktail mixture containing selective substrates for seven individual P450 activities (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4). The assay can be applied to both freshly isolated and cryopreserved hepatocyte suspensions, and the results are available within 1 h, which could help to make short-term decisions: 1) to assess the suitability for cell transplantation of a preparation of freshly isolated hepatocytes or a particular batch of thawed cells, or 2) to estimate the convenience of banking a particular cell preparation.

1976 ◽  
Vol 160 (2) ◽  
pp. 205-209 ◽  
Author(s):  
S Briggs ◽  
R A Freedland

1. In hepatocytes isolated from 24 h-starved rats, urea production from ammonia was stimulated by addition of lactate, in both the presence and the absence of ornithine. The relationship of lactate concentration to the rate of urea synthesis was hyperbolic. 2. Other glucose precursors also stimulated urea production to varying degrees, but none more than lactate. Added oleate and butyrate did not stimulate urea synthesis. 3. Citrulline accumulation was largely dependent on ornithine concentration. As ornithine was increased from 0 to 40 mM, the rate of citrulline accumulation increased hyperbolically, and was half-maximal when ornithine was 8-12 mM. 4. The rate of citrulline accumulation was independent of the presence of lactate, but with pyruvate the rate increased. 5. The rate of urea production continued to increase as ornithine was varied from 0 to 40 mM. 6. It was concluded that intermediates provided by both ornithine and lactate are limiting for urea production from ammonia in isolated liver cells. It was suggested that the stimulatory effect of lactate lies in increased availability of cytosolic aspartate for condensation with citrulline.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 370
Author(s):  
Umair Iqbal ◽  
Ravirajsinh N. Jadeja ◽  
Harshit S. Khara ◽  
Sandeep Khurana

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis.


2007 ◽  
Vol 87 (5) ◽  
pp. 1200-1207 ◽  
Author(s):  
Patricia Fauque ◽  
Anis Ben Amor ◽  
Christiane Joanne ◽  
Germain Agnani ◽  
Jean Luc Bresson ◽  
...  

Author(s):  
Lu Zhai ◽  
Yuhua Liu ◽  
Rongrui Huo ◽  
Zhaofang Pan ◽  
Juan Bin ◽  
...  

Background: Allogeneic haematopoietic stem cell transplantation (ALLO-HSCT) is a potentially curative approach to treat β-thalassemia major (β-TM). Objective and Methods: To assess the quality of life (QOL) of patients with β-TM after ALLO-HSCT, we searched PubMed, Embase, Web of Science, and Medline for articles on the quality of life (QOL) of patients with β-TM from 1 Feb 2020 to 31 Mar 2020. Results: Our review revealed that the QOL of patients with β-TM after ALLO-HSCT from a sibling donor is higher than that of patients that received blood infusion and iron-chelating therapy. Survivors of ALLO-HSCT have a QOL as good as that of a healthy population and the ability to return to normal life. However, studies thus far are limited to investigations with a few patients with β-TM who received ALLO-HSCT of the bone marrow (BM) from a sibling donor or related donor. Graft vs. host disease, patient age, gender, sexual desire, health condition, psychological state, financial and employment stress, and social support contributed to a worse QOL after ALLO-HSCT. Medicine usage, physical therapy, and psychological intervention may help improve the decline in QOL related to ALLO-HSCT in patients with β-TM. Conclusion: Doctors and nurses must focus on implementing medicine usage, physical therapy and psychological intervention to improve the decline in QOL related to ALLO-HSCT.


1995 ◽  
Vol 268 (1) ◽  
pp. G183-G188 ◽  
Author(s):  
J. Stadler ◽  
D. Barton ◽  
H. Beil-Moeller ◽  
S. Diekmann ◽  
C. Hierholzer ◽  
...  

Inflammatory stimulation of the liver is known to induce nitric oxide (NO) biosynthesis. NO can interfere with the activity of a number of enzymes important to cellular metabolism. This study was carried out to investigate the influence of NO on rat hepatocyte glucose output and urea production. Induction of NO synthesis by incubation with a combination of cytokines and lipopolysaccharide led to a 48.8 +/- 2.4% inhibition of glucose output and to a 45.0 +/- 6.4% suppression of urea production. Inhibition of NO synthesis with NG-monomethyl-L-arginine was able to totally prevent these effects. High concentrations of L-arginine overcame the inhibition of urea production caused by endogenous NO synthesis. Exposure of HC to NO donors resulted in a concentration-dependent inhibition of glucose output, without having any effect on urea production. Hepatocellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was also found to be inhibited by endogenously produced NO (33.5 +/- 5.2%), as well as by exogenously applied NO. However, an exact correlation between GAPDH activity and glucose output could not be established. These data indicate that NO biosynthesis may contribute to the development of hepatic dysfunction in chronic sepsis.


Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2604-2613 ◽  
Author(s):  
Joachim Wiskemann ◽  
Peter Dreger ◽  
Rainer Schwerdtfeger ◽  
Andrea Bondong ◽  
Gerhard Huber ◽  
...  

Abstract Before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients experience considerable physical and psychologic distress. Besides graft-versus-host disease and infections, reduced physical performance and high levels of fatigue affect patients' quality of life. This multicenter randomized controlled trial examined the effects of a partly self-administered exercise intervention before, during, and after allo-HSCT on these side effects. After randomization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission, during inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical performance, quality of life, and physical/psychologic distress were measured by standardized instruments at baseline, admission to, and discharge from hospital and 6 to 8 weeks after discharge. The exercise group showed significantly improvement in fatigue scores (up to 15% improvement in exercise group vs up to 28% deterioration in control; P < .01-.03), physical fitness/functioning (P = .02-.03) and global distress (P = .03). All effects were at least detectable at one assessment time point after hospitalization or repeatedly. Physical fitness correlated significantly with all reported symptoms/variables. In conclusion, this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT. Because of low personnel requirements, it might be valuable to integrate such a program into standard medical care.


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