Analysis of Cell Cycle Compartments of Hepatocytes After Partial Hepatectomy

Abstract

An analysis of cell kinetic parameters as a function of intralobular localization of hepatocytes was performed using autoradiographic methods to obtain a basis for a quantitative description of cell cycle compartments after partial hepatectomy. The influx into the S compartment revealed a maximum in a lobular zone not immediately adjacent to the portal tract, with a decrease towards the perivenous and periportal area of the lobule. The maximum influx was found in the intermediate zone at 34 hr and a lower one in the perivenous parts of the lobule at 40 hr. The influx pattern at 56 hr was similar to the situation at 18 hr. The fraction of labelled mitoses in the whole liver and in subunits of the lobule disclosed a constant duration of S whereas the duration of G2+ M was prolonged from the periportal to the perivenous zone. A graphical model of kinetic events after partial hepatectomy is proposed, which describes the sizes of the various cell cycle compartments; the model successfully predicted the results of a continuous labelling experiment.

Retroviral-mediated gene transfer into hepatocytes in vivo.

“…This suggested that most of those cycling hepatocytes that integrated the vector underwent less than two subsequent cell divisions. Because the duration ofthe adult rat hepatocyte cell cycle is 33 hr (13) and the regeneration process generally proceeds for about 7 days (12,22), our observation supports the notion that most hepatocytes participate in regeneration. The numbers of infected hepatocytes were higher when the virus perfusions were performed during the peak of DNA synthesis at 24 hr.…”

“…On the other hand, partial resection of the liver is followed by a regenerative phase that rapidly reconstitutes a full-size organ. Many hepatocytes enter the cell cycle during this process (12,13) and should be susceptible to retrovirus infection at this time. After complete restoration of the organ weight, hepatocytes return to a quiescent state (12,13), and prolonged persistence of infected cells may be expected.…”

“…Many hepatocytes enter the cell cycle during this process (12,13) and should be susceptible to retrovirus infection at this time. After complete restoration of the organ weight, hepatocytes return to a quiescent state (12,13), and prolonged persistence of infected cells may be expected. Therefore, the in situ infection of hepatocytes with recombinant retroviral vectors may be a suitable method for long-term complementation of a genetic defect.…”

“…The numbers of infected hepatocytes were higher when the virus perfusions were performed during the peak of DNA synthesis at 24 hr. At this time, the fraction of cells undergoing DNA synthesis is estimated to be 15% (12), and 30%o of the hepatocytes enter the cell cycle during the next 12 hr (13) ing the effects of more concentrated virus stocks, increased perfusion times, and addition of hepatocyte growth factors (23,24) to the perfusion medium.…”

Liver regeneration after partial hepatectomy is non-uniform: flow cytometric bromodeoxyuridine incorporation and cell cycle studies in a porcine model

“…Studies on liver regeneration after surgical resection have mainly been carried out on small experimental animals, such as rats and rabbits [3][4][5]. Similar data on larger animals is scarcely available.…”