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Bone marrow derived liver stem cells (BDLSC) engraft more efficiently livers undergoing rejection than hepatocytes: a potential novel therapeutic approach for the treatment of liver rejection
No full textBACKGROUND: The definitive therapy for end-stage liver disease is orthotopic liver transplantation (OLT). However, rejection is still a major cause of mortality and morbidity following OLT. Hepatocyte transplantation has been used experimentally to treat liver diseases. The aim of this study was to investigate whether bone marrow-derived liver stem cells (BDLSC) and mature hepatocytes could repopulate transplanted livers undergoing rejection.
METHODS: OLT was carried out from D'Agouti (C3-positive female) into Lewis (C3-negative female) rats. BDLSC were transplanted from Lewis (male) into livers of D'Agouti (female) rats. Group A (n = 9) received intraportal normal saline. Groups B (n = 9) and C (n = 9) underwent intraportal transplantation of mature hepatocytes (Lewis female, 0.75 x 10(7)) and DBLSC (Lewis male, 5 x 10(4)) respectively. All groups received subtherapeutic immunosuppression (Cyclosporin 0.25 mg/kg/d) for 13 days. Liver repopulation was assessed using immunohistochemistry (C3 antigen-negative cells), in-situ hybridization, (Y-chromosome-positive BDLSC) and histologic assessment (hematoxylin and eosin) for rejection.
RESULTS: BDLSC and mature hepatocytes repopulated 62 +/- 12.3% and 2.5 +/- 1.7% of rejecting livers, respectively. BDLSC demonstrated formation of hepatic lobules and portal triads with little evidence of rejection 36 days after discontinuation of immunosuppression.
CONCLUSIONS: BDLSC can repopulate livers undergoing severe rejection. Moreover, BDLSC can differentiate into hepatocytes and cholangiocytes. This finding may have important clinical implications
SERUM BILE-ACID LEVELS IN PATIENTS WITH FULMINANT HEPATIC-FAILURE (FHF) TREATED WITH A BIOARTIFICIAL LIVER (BAL)
No full textIn vitro morphological and functional characterization of isolated porcine hepatocytes for extracorporeal liver support: bile acid uptake and conjugation.
No full textRecently, researchers have focused on the use of bioartificial liver (BAL) to support patients with fulminant hepatic failure (FHF). We have developed a cell-based BAL, consisting of porcine hepatocytes in a hollow- fiber bioreactor. To better characterize BAL metabolic functions in vitro, bioreactors were inoculated with 48-h-cultured, microcarrier-attached hepatocytes and perifused with recirculating human plasma that contained either 1 μCi of [24-14C] plasma-enriched cholate or 1 μCi of [24-14C] plasma-enriched taurocholate. Bile acids were sampled hourly and separated into four fractions (unconjugated, glycoconjugated, tauroconjugated, and sulfated) for radioactivity determination. Following 3 h perifusion, the glycoconjugated and sulfated bile acid fractions in the bioreactor extrafiber space were significantly elevated when compared to the recirculating plasma. During perifusion with taurocholate-enriched plasma, a relative decrease in the tauroconjugated fraction and an increase..
Growth of intraportally transplanted islets under liver regeneration stimulus and restoration of normoglycemia in streptozocin-diabetic rats
No full textBackground. Limitation of β-cell growth after intraportal islet transplantation plays an important role in graft failure. To induce transplanted β-cell proliferation, we studied the effect of compensatory liver growth in diabetic rats that had a subtherapeutic islet mass previously injected into the liver. Methods. Syngeneic rats were used as islet donors or recipients; diabetes was induced by streptozocin. Three groups of streptozocin-treated rats were studied. In group 1, 250 islets were selectively transplanted into the posterior liver lobes and 10 days later anterior portal branch ligation (PBL) was performed (n - 18); in group 2, 250 islets were transplanted into the posterior lobes and 10 days later sham PBL was performed (n = 13); in group 3, rats underwent a sham transplantation and PBL (n = 6). Nonfasting blood glucose levels and body weight were monitored. Six rats in groups 1 and 2 were killed 48 hours after PBL, liver sections were stained for proliferating cell nuclear antigen, and islet cell labeling index was calculated. The remaining rats were killed 30 days later. Liver compensatory growth or atrophy was calculated and morphometric determination of β-cell area was assessed on insulin-immunostained sections of the liver. Results. In group 1 rats killed 48 hours after PBl, islet cell labeling index was significantly higher than in group 2 (p < 0.0001). After PBL, we observed normalization of nonfasting blood glucose levels in 10 of 12 rats. At 30 days, posterior liver lobes showed compensatory growth (218.5% ± 18.6%) accompanied by atrophy of the anterior lobes; morphometric study of liver- engrated islets showed a significant increase of individual β-cell area, compared with group 2 (p < 0.0001). In groups 2 and 3, normoglycemia was not achieved. Conclusions. In streptozocin-diabetic rats, normoglycemia was restored after transplantation of a sub-therapeutic islet mass, followed by PBL-induced liver regeneration. Histologic and morphometric results indicating islet cell proliferation suggest that compensatory liver growth might have induced a hypertrophic/hyperplastic response in the intraportally transplanted β-cells
Hepatic regeneration induces normoglycemia in diabetic rats previously transplanted into the liver with a subtherapeutic islet mass
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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