Hepatic stellate cells – from past till present: morphology, human markers, human cell lines, behavior in normal and liver pathology

Abstract

Hepatic stellate cell (HSC), initially analyzed by von Kupffer, in 1876, revealed to be an extraordinary mesenchymal cell, essential for both hepatocellular function and lesions, being the hallmark of hepatic fibrogenesis and carcinogenesis. Apart from their implications in hepatic injury, HSCs play a vital role in liver development and regeneration, xenobiotic response, intermediate metabolism, and regulation of immune response. In this review, we discuss the current state of knowledge regarding HSCs morphology, human HSCs markers and human HSC cell lines. We also summarize the latest findings concerning their roles in normal and liver pathology, focusing on their impact in fibrogenesis, chronic viral hepatitis and liver tumors.

Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)

“…In 1876, Carl von Kupffer first described HSCs in a letter to his colleague Waldeyer, in which he named these cells 'Sternzellen or stellate cells' [19][20][21]. HSCs, previously known as perisinusoidal cells, lipocytes, Ito cells and fat storing cells, are liver resident non-parenchymal cells that perform a wide range of physiological and pathological functions [14,[20][21][22][23]. In the normal liver, HSCs represent 5-8% of the total hepatic cells and are localized in the space of Disse between sinusoidal endothelial cells and the basolateral surface of hepatocytes [14,[20][21][22][23][24].…”

“…HSCs, previously known as perisinusoidal cells, lipocytes, Ito cells and fat storing cells, are liver resident non-parenchymal cells that perform a wide range of physiological and pathological functions [14,[20][21][22][23]. In the normal liver, HSCs represent 5-8% of the total hepatic cells and are localized in the space of Disse between sinusoidal endothelial cells and the basolateral surface of hepatocytes [14,[20][21][22][23][24]. In human liver, there are approximately 10 HSCs per 100 hepatocytes and in rat liver approximately 13 HSCs per 100 parenchymal cells [20].…”

“…A distinct characteristic feature of quiescent HSCs in healthy liver is the cytoplasmic storage of retinoid (vitamin A and its metabolites) within lipid droplets [14,[22][23][24]26,27]. Approximately 80-90% of hepatic retinoids are stored in HSC lipid droplets [22,23]. HSCs play a major role in the uptake, storage and metabolism of vitamin A or retinol [20,23,28].…”

“…Approximately 80-90% of hepatic retinoids are stored in HSC lipid droplets [22,23]. HSCs play a major role in the uptake, storage and metabolism of vitamin A or retinol [20,23,28]. Dietary retinol once absorbed in the gut is esterified to retinyl esters, packaged in chylomicrons and transported to the liver, where hepatocytes take up the retinol-containing chylomicrons [22,23,29].…”

“…HSCs play a major role in the uptake, storage and metabolism of vitamin A or retinol [20,23,28]. Dietary retinol once absorbed in the gut is esterified to retinyl esters, packaged in chylomicrons and transported to the liver, where hepatocytes take up the retinol-containing chylomicrons [22,23,29]. Upon uptake by hepatocytes, the retinyl esters are metabolized to retinol and subsequently transferred to HSCs, with the help of the cellular retinol binding protein (CRBP-1) [23,30,31].…”