Elsevier

Transplantation Proceedings

Volume 41, Issue 10, December 2009, Pages 4401-4404
Transplantation Proceedings

Experimental transplantation
Other models
Expression of Mesenchymal, Hematopoietic, and Biliary Cell Markers in Adult Rat Hepatocytes After Partial Hepatectomy

https://doi.org/10.1016/j.transproceed.2009.09.082Get rights and content

Abstract

Background and Purpose

It has been suggested that liver regeneration can occur either by differentiated adult hepatocytes which retain the capability for several rounds of replication or by hepatic progenitor cells, depending on the number of hepatocytes lost. We sought to study the differentiation potential of hepatocytes following partial hepatectomy (PH) in rats.

Methods

Using immunohistochemistry and confocal microscopy we studied the distribution of cytokeratin 7 (CK7), CK19, vimentin, desmin, CD34, and c-kit among adult rat liver hepatocytes after PH at various times just after hepatectomy and after 8, 16, 24, 36, 48, and 60 hour and 6 and 16 days.

Results

Vimentin, c-kit, and desmin positivity were observed in regenerating hepatocytes in the early stages. Desmin and vimentin staining were also demonstrated in stellate cells. Staining enhancement in stellate cells progressed from day 3 to day 6. No liver sections were stained positive for CD34, CK19, or CK7.

Conclusion

After PH, mature hepatocytes revealed their potential to regain the markers that they do not express when they are quiescent. This result supported the plasticity and differentiation potential of adult hepatocytes during regeneration.

Section snippets

Animals

The experiments were approved by our Ethical Committee on the Use and Care of Animals and performed according to international guidelines. Nine male Wistar albino rats weighing 250–300 g were maintained in free-standing cages, acclimatized to normal laboratory conditions and fed a standard rat pellet diet with tap water ad libitum. On the day of surgery we allowed only water.

Surgical Procedures

Anesthesia induced with subcutaneous ketamine hydrochloride (100 mg/kg) was maintained with isoflurane inhalation. The

Results

Upon macroscopic inspection, the daily assessment of the remnant liver tissue showed a gradual increase in hepatic mass from the first postoperative day to complete recovery by the sixth day.

Animals killed just after hepatectomy were studied as controls Liver parenchyma of control rats showed a typical sinusoidal architecture with a normal hepatocellular structure and an absence of mitotic figures. In control specimens, hepatocytes did not stain with any of the markers: CD34, c-kit, vimentin,

Discussion

Hepatic stem/progenitor cells, also known as oval cells, have been implicated in hepatic tissue repair in rodents, at a time when the capacity for hepatocyte and bile duct replication was exhausted or experimentally inhibited.17 In multiple independent studies, these oval cells have been shown to share moleculer markers with adult hepatocyes (albumin, CK8, and CK18), bile duct cells (CK7, CK19, OV-6, and A6), fetal hepatoblasts (AFP), and hematopoietic stem cells (Thy-1, Sca-1, and c-kit).8, 15

References (30)

  • G.K. Michalopoulos et al.

    Liver regeneration

    Science

    (1997)
  • V. Ankoma-Sey

    Hepatic regeneration–revisiting the myth of prometheus

    News Physiol Sci

    (1999)
  • Y. Zang et al.

    Hepatic stem cells: existence and origin

    World J Gastroenterol

    (2003)
  • S. Matsusaka et al.

    Hepatology

    (1999)
  • U. Baumann et al.

    Expression of the stem cell factor c-kit in normal and diseased pediatric liver

    Hepatology

    (1999)
  • Cited by (3)

    • Viability, function and morphological integrity of precision-cut liver slices during prolonged incubation: Effects of culture medium

      2015, Toxicology in Vitro
      Citation Excerpt :

      It is known that BECs produce cytokines, which stimulate fibroblasts proliferation and differentiation towards MFs leading to the deposition of extracellular matrix in portal areas (Guyot, 2007b). Besides proliferation and differentiation of PFs towards MFs, an activation of HSCs was observed, that was supported by an increase in the intensity of vimentin, desmin and α-SMA staining (Kara et al., 2009). Also the collagen I and collagen III data are in line with the findings of the desmin and α-SMA staining, as collagen deposition prevailed in the areas of bile duct proliferation.

    • The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane

      2011, Journal of Biological Chemistry
      Citation Excerpt :

      This was confirmed in this study; SU6656 inhibited both hyperosmotic Yes and Fyn activation, whereas PP-2 inhibited Fyn but not Yes phosphorylation upon hyperosmotic exposure in the perfused rat liver (Fig. 2B). Although SU6656 and PP-2 may also inhibit c-kit and abl, an involvement of these kinases is unlikely because both kinases may be found in hepatocellular tumors or in the regenerating liver but are not expressed in normal hepatocytes (40, 41). In addition to Src kinases, also the MAP kinases Erk, p38MAPK, and JNK are regulated by anisoosmolarity as shown in primary rat hepatocytes (21, 23).

    • Genome-wide expression profiling of hepatic oval cells after partial hepatectomy in rats

      2011, Tissue and Cell
      Citation Excerpt :

      Oval cells are a population of small cells morphologically characterized by an oval-shaped nucleus and a high nucleus–cytoplasm ratio (Viebahn and Yeoh, 2008). It has been shown that these cells share the molecular markers with hepatocytes (ALB, AFP, γ-GT, G6PC, etc.), biliary epithelial cells (CK7, CK19, etc.), predicting that they have potentials to differentiate into hepatocytes and biliary epithelial cells (Kara et al., 2009). Activation, proliferation and differentiation of oval cells are tightly controlled by some liver regeneration (LR)-related factors, such as growth factors, cytokines and others (Almeida-Porada et al., 2010).

    View full text