Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease

Abstract

Considering that the heterogenic population of a hepatic progenitor cell line (HPCL) can play a vital role in autoimmune hepatitis (AIH), we decided to conduct pioneering retrospective evaluation of these cells in pediatric AIH by means of transmission electron microscopy (TEM). The aim of the study was to assess the ultrastructure of the HPCL in children with untreated AIH. Ultrastructural analysis of the HPCL population, preceded by immunohistochemical staining for cytokeratin 7 (CK7), was performed using pretreatment liver biopsies from 23 children with clinicopathologically diagnosed AIH. Immunohistochemical assessment for CK7 allowed detection of proliferating immature epithelial cells differentiating towards periportal and intralobular intermediate hepatocytes without marked formation of ductular reactions in AIH children. Using TEM, we distinguished three morphological types of HPCs: I—the most undifferentiated progenitor cells; III—intermediate hepatocyte-like cells; II—intermediate bile duct cells. Most frequent were the cells differentiating towards hepatocytes, most rare—those differentiating towards cholangiocytes. The results indicate that an HPCL may be an important source of hepatocyte regeneration. Ultrastructural analyses of the HPCL population, combined with immunohistochemistry for CK7, might be a useful tool to evaluate liver cell regeneration, including fibrogenesis, and may help better understand the morphological pattern of the disease, in pediatric AIH. Frequent appearance of an HPCL in the vicinity of fibrotic foci, often accompanied by hyperactive Kupffer cells and transitional hepatic stellate cells, may indicate their significant involvement in liver fibrogenesis.

Liver Regeneration and Cell Transplantation for End-Stage Liver Disease

“…As determined in various liver diseases in humans and animal models, there are hepatocytes with BECs markers that emerge ectopically in the parenchymal region of the liver [ 18 , 19 , 20 , 21 ]. These intermediate cells are thought to be derived from LPCs from biliary compartment.…”

Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases

“…With the potential for self-renewal and differentiation plasticity, hepatic and extrahepatic stem cells are attracting much attention in regenerative medicine. Among them, multipotent stem cells are the most widely studied [3,4]. However, some challenges must be resolved before stem cells can be used in routine clinical practice.…”