The development of hepatic stellate cells in normal and abnormal human fetuses - an immunohistochemical study.
The precise embryological origin and development of hepatic stellate cells is not established. Animal studies and observations on human fetuses suggest that they derive from posterior mesodermal cells that migrate via the septum transversum and developing diaphragm to form submesothelial cells beneath the liver capsule, which give rise to mesenchymal cells including hepatic stellate cells. However, it is unclear if these are similar to hepatic stellate cells in adults or if this is the only source of stellate cells. We have studied hepatic stellate cells by immunohistochemistry, in developing human liver from autopsies of fetuses with and without malformations and growth restriction, using cellular Retinol Binding Protein-1 (cRBP-1), Glial Fibrillary Acidic Protein (GFAP), and α-Smooth Muscle Actin (αSMA) antibodies, to identify factors that influence their development. We found that hepatic stellate cells expressing cRBP-1 are present from the end of the first trimester of gestation and reduce in density throughout gestation. They appear abnormally formed and variably reduced in number in fetuses with abnormal mesothelial Wilms Tumor 1 (WT1) function, diaphragmatic hernia and in ectopic liver nodules without mesothelium. Stellate cells showed similarities to intravascular cells and their presence in a fetus with diaphragm agenesis suggests they may be derived from circulating stem cells. Our observations suggest circulating stem cells as well as mesothelium can give rise to hepatic stellate cells, and that they require normal mesothelial function for their development.
Department of Anatomical Pathology, Prince of Wales Hospital, Randwick Sydney, NSW, Australia Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Discipline of Pathology, School of Medicine, University of Western Sydney, Sydney, NSW, Australia.
Christine K C
CK
Loo
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Tamara N
TN
Pereira
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Katarzyna N
KN
Pozniak
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Mette
M
Ramsing
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Ida
I
Vogel
Hepatic Fibrosis Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Faculty of Medicine and Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia Grant.Ramm@qimrberghofer.edu.au.
Grant A
GA
Ramm
Circulating stem cells; GFAP; Mesothelium; cRBP‐1; diaphragm