The Role of Hepatotrophic Stimulation in Heterotopic Hepatocyte Transplantation

1993 ◽  
Vol 331 ◽  
Author(s):  
P.-M. Kaufmann ◽  
S. Uyama ◽  
K. Sano ◽  
D. Mooney ◽  
J. P. Vacanti

AbstractIn the future, the development of methods for transplantation of large hepatocyte numbers could provide an alternative to the established liver and split liver transplantation. The use of three dimensional prevascularized polyvinyl alcohol (PVA) scaffolds have allowed hepatocyte transplantation equivalent to a whole liver mass. This study was designed to determine if a portacaval-shunt (PCS) or a 70% hepatectomy (70% HE) enhanced engraftment and proliferation of transplanted hepatocytes in heterotopic locations.Male Lewis rats served as both donors and recipients, respectively. PVA-sponges were implanted as matrices for the transplanted hepatocytes. Recipient animals were divided into four groups. All groups received transplantation of 5×107 Hepatocytes (HCTx). In addition, group A received 70% HE, group B received a PCS plus 70% HE whereas group D received PCS. Group C as a control, received only HCTx. Quantitative morphometric analysis of hepatocyte area was performed on day 0, 3, 7 and 14 after transplantation. BrdU staining was performed to study DNA-Synthesis in the graft on day 3 and 14.PCS alone and in combination with a partial hepatectomy led to significantly greater cell area one week after transplantation compared to the partial hepatectomy alone. 70% HE resulted in significantly larger cell area than the controls. At two weeks after transplantation, these significant differences persisted with the exception of Group A and C results which were not significantly different. On day 3, BrdU staining revealed a significantly higher DNA synthesis rate in Groups A and B compared to Group C. On day 14, no statistically significant differences in levels of DNA synthesis could be observed.We conclude that hepatocytes can be successfully transplanted into PVA-devices. Engraftment and proliferation can be significantly enhanced by using portacaval shunt and partial hepatectomy as hepatotrophic stimulation.

1961 ◽  
Vol 39 (6) ◽  
pp. 1043-1054 ◽  
Author(s):  
D. K. Myers ◽  
C. Anne Hemphill ◽  
Constance M. Townsend

Deoxycytidylate deaminase activity and net synthesis of deoxyribonucleic acid (DNA) in vivo were found to increase at approximately the same time during the early stages of liver regeneration. However, deaminase activity in the regenerating liver remained at a high level for 1 day after DNA synthesis had slowed down again during the later stages of regeneration. The increase in deaminase activity was restricted as a result of exposure to 600 r X radiation during early regeneration, but this effect only became evident 11–16 hours after the irradiation. Irradiation on the second day after partial hepatectomy, when deaminase levels in control regenerating livers were relatively constant, failed to affect the deaminase activity immediately but did produce a 40–50% decrease in activity 11–16 hours later. Other antimitotic agents, e.g., colchicine, had little effect on deaminase activity.


2000 ◽  
Vol 20 (1) ◽  
pp. 55-56
Author(s):  
Liao Jiazhi ◽  
Tang Wangxian ◽  
Wang Junping ◽  
Zhang Wenying

1990 ◽  
Vol 51 (3-4) ◽  
pp. 265-267 ◽  
Author(s):  
Lina Matera ◽  
Alessandra Cesano ◽  
Giampiero Muccioli ◽  
Fabrizio Veglia

1987 ◽  
Vol 72 (4) ◽  
pp. 455-461 ◽  
Author(s):  
Rieko Nakata ◽  
Ikuyo Tsukamoto ◽  
Masamitsu Miyoshi ◽  
Shosuke Kojo

1. Thyroparathyroidectomy (TPTX) carried out at 72 h before partial hepatectomy (PH) reduced the induction of hepatic thymidylate synthetase (TS) and thymidine kinase (TK), which are rate-determining enzymes in DNA synthesis, at 24 h after PH. 2. When TPTX was carried out at 24 h before PH, TK activity at 24 h after PH was not reduced at all, yet TS activity was reduced significantly. Thus the effect of TPTX differed in time dependence between TS and TK. 3. The depression of TK activity in rats which were subjected to TPTX at 72 h before PH, was recovered by Ca2+ supplementation. This result demonstrated that the rise of TK activity in regenerating liver is regulated by plasma Ca2+. 4. Since a high dose of tri-iodothyronine (T3) was required to cause elevation of the activities of these enzymes and DNA content in 24 h-regenerating liver of TPTX rats, the relative contribution of T3 to liver regeneration may be small.


1987 ◽  
Vol 87 (5) ◽  
pp. 635-641
Author(s):  
M.H. Navarrete ◽  
A. Cuadrado ◽  
M. Escalera ◽  
J.L. Canovas

The variability of (1) surface area projection (size) at which cells terminate DNA replication, (2) the area at which they initiate mitosis, (3) the area at which they divide, (4) the duration of G2, and (5) the duration of G2 plus mitosis (in fact, prophase + metaphase + anaphase) has been estimated in steady-state cell populations of Allium cepa root meristems. The coefficient of variation of cell area at termination of DNA synthesis was found to be 14% while the coefficient of variation of cell area at mitosis initiation was 13%. As there is also a substantial variability of G2 (the coefficient of variation was estimated to be 38%), the combination of these data indicates that cell size regulation of G2 contributes to maintaining cell size variability (and therefore DNA concentration) within certain limits. Mitosis also varies but less than G2 (the coefficient of variation of G2 + mitosis was found to be 31%). As the coefficient of variation of cell area at division (14%) is hardly larger than the coefficient of variation of cell area at initiation of mitosis, it can be suggested that coordination between cell size and mitosis duration helps to avoid a significant increase in the variability of cell size at the end of the division cycle.


1985 ◽  
Vol 249 (5) ◽  
pp. R563-R569 ◽  
Author(s):  
R. P. Cornell

The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient. All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats. We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.


Sign in / Sign up

Export Citation Format

Share Document