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Objectives: To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location.
Methods: Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), pi-class glutathione S-transferase (GST-pi), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohistochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls.
Results: Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called "typical ductular proliferation (ADP)" or "typical ductular reaction" in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST-pi, CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST-pi, and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients (chi2= 63.62, P<0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients.
Conclusion: In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.
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J Hepatol
December 2024
The Concern Foundation Laboratories at The Lautenberg Center for Immunology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:
Background And Aims: RORc-expressing immune cells play important roles in inflammation, autoimmune disease and cancer. They are required for lymphoid organogenesis and have been implicated in tertiary lymphoid structure (TLS) formation. TLSs are formed in many cancer types and have been correlated with better prognosis and response to immunotherapy.
View Article and Find Full Text PDFJ Clin Invest
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPC) contribute to tissue regeneration after severe hepatic injury yet signals instructing progenitor cell dynamics and fate are largely unknown. The Tissue Inhibitor of Metalloproteinases, TIMP1 and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Department of Pediatrics, Qilu Hospital of Shandong University, 107 Wenhua Xilu, Jinan, 250012, Shandong, P.R. China.
Background: Hepatic organoids (HOs), validated through comparative sequencing with human liver tissues, are reliable models for liver research. Comprehensive transcriptomic and proteomic sequencing of HOs throughout their induction period will enhance the platform's utility, aiding in the elucidation of liver development's molecular mechanisms.
Methods: We developed hepatic organoids (HOs) from embryonic stem cells (ESCs) through a de novo induction protocol, mimicking the stages of fetal liver development: ESCs to definitive endoderm (DE), then to foregut (FG), hepatoblasts (HB), and finally to HOs stage 1 (HO1), culminating in self-organizing HOs stage 2 (HO2) via dissociation and re-inoculation.
J Surg Case Rep
December 2024
Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, 4006, QLD, Australia.
Pancreatic neuroendocrine neoplasms are currently thought to originate from distinct progenitor cells that cannot differentiate into each other. We present the first reported case of a combined pancreatic neuroendocrine tumour and neuroendocrine carcinoma in a 58-year-old man who was investigated for abdominal pain and constipation. Imaging revealed a large left upper quadrant mass infiltrating the pancreatic body and tail, splenic hilum, and posterior stomach wall, with five hepatic metastases.
View Article and Find Full Text PDFActivation of brown and beige fat biogenesis promotes metabolic health in rodents and humans, but typically requires cold exposure or pharmacological activation of β-adrenergic receptors, which may pose cardiovascular risks. Dietary intervention represents a clinically viable alternative strategy to induce beige cells and thus enhance metabolic health, though the underlying mechanisms remain poorly understood. In this study, we identified specific microbiota members in both mice and humans that promote browning of white adipose tissue (WAT) and ameliorate metabolic disorders in the context of a low-protein diet (LPD).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!