: In PH, PLTX, although ideal in theory, is rarely achieved. Patients usually have reached end‐stage kidney disease while requiring combined liver and kidney transplantation. In this combined ...procedure, the sudden high oxalates mobilization from blood and tissue stores jeopardizes the success of the kidney graft, with a high risk of post‐transplant early kidney necrosis or chronic graft damage. Here, we report the case of a three‐yr‐old girl with PH and ESRF in whom we performed sequentially deceased donor liver transplantation followed four months later by living donor kidney transplant, after normalization of blood oxalate levels and improvement of urinary oxalate output. After this two‐step transplantation, our patient showed normalization of renal function with good urinary output and maintained normal blood oxalate levels. This strategy seems to be a reasonable approach in order to avoid acute renal tubular injury because of oxalate excretion in these patients.
A 3-year-old girl suffering from ornithine carbamoyltransferase (OTC) deficiency was poorly equilibrated under conventional diet and scavenger treatment. Following unsuccessful cryopreserved ...hepatocyte transplantation, she received two infusions of Adult Derived Human Liver Stem/Progenitor Cells (ADHLSCs) expanded in vitro under GMP settings, the quantity being equivalent to 0.75% of her calculated liver mass. Using FISH immunostaining for the Y chromosome, the initial biopsy did not detect any male nuclei in the recipient liver. Two liver biopsies taken 100 days after ADHLSC transplantation showed 3% and 5% of male donor cells in the recipient liver, thus suggesting repopulation by donor cells. Although limited follow-up did not allow us to draw conclusions on long-term improvement, these results provide a promising proof of concept that this therapy is feasible in an OTC patient.
Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term ...partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.
Epstein-Barr virus (EBV) was the first herpes virus described as being oncogenic in humans. EBV infection is implicated in post-transplant lymphoproliferative diseases (PTLD) and several other ...cancers in non-immunocompromised patients, with more than 200,000 new cases per year. While prevention of PTLD is improving, mainly based on EBV monitoring and preemptive tapering of immunosuppression, early diagnosis remains the best current option for the other malignancies. Significant progress has been achieved in treatment, with decreased mortality and morbidity, but some challenges are still to face, especially for the more aggressive diseases. Possible prevention by EBV vaccination would be a more global approach of this public health problem, but further active research is needed before this goal could be reached.
The current majority of protocols for hepatocyte differentiation of mesenchymal stem cells (MSCs) are conducted using oncostatin M (OSM) as an inducer of hepatocyte-like maturation. As leukemia ...inhibitory factor (LIF) and OSM share similar signaling pathways, we examined whether LIF could play a role in the hepatocyte differentiation process. A differentiation protocol was designed using LIF as a maturation cytokine and this was compared with standard and control protocols applied to human MSCs of bone marrow origin. We observed that mesenchymal-derived hepatocyte-like cells (MDHLCs) acquired similar morphological changes when exposed to LIF or to OSM. Using protein and gene expression assays, we noticed a comparable hepatic marker expression in both differentiation conditions. Furthermore, LIF and OSM allowed the acquisition of equivalent levels of hepatocyte-like functionality as attested by evaluation of urea secretion and glycogen deposition. However, no increase in the expression of hepatocyte-like features could be observed in MDHLCs after a combined exposition to LIF and OSM. In conclusion, we demonstrated that LIF can play a similar role as OSM in the hepatocyte differentiation process of human MSCs.
: A case of liver transplantation for HCC complicating BA in an eight‐month old infant is reported. HCC in BA is extremely rare. Screening of AFP and ultrasonographic examination should be performed ...regularly in patients with secondary biliary cirrhosis for early detection of HCC.
Liver cell isolation and transplantation have been successfully performed in animal models and in humans. However, lack of initial engraftment due to cell death is a major roadblock to achieving ...clinical significance. Apoptosis was recently identified as an important cause of freshly isolated and banked hepatocyte cell death Cell Transplant. 10 (2001) 59. Pathways involving detachment-induced apoptosis (anoikis) are well characterized in other cell types. Loss of cell anchorage occurs during the hepatocyte isolation procedure prior to cell transplantation, but little is known about the role of this pathway in the survival of isolated hepatocytes. We report early occurrence of anoikis in primary mouse hepatocytes cultured under detached conditions on glass plates as compared to under attached conditions on plastic plates. Apoptosis in detached cells was determined using complementary techniques (DNA laddering, cell death ELISA assay, TUNEL assay and morphological analysis) and was detected as early as 15 min after culture under detached conditions. Further analysis of the mechanisms inducing apoptosis during liver cell isolation and transplantation and of ways to prevent them could lead to improved clinical protocols of liver cell therapies.
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