Stellate Cells and Fibrosis

When healing turns into killing – the pathophysiology of pancreatic and hepatic fibrosis

“…In the initiation phase, HSCs become exposed to inflammatory mediators released from damaged liver cells (Dewidar et al., 2019; Foglia et al., 2019; Liu et al., 2009): for example, platelet‐derived growth factor (PDGF), transforming growth factor β (TGF‐β), or redox‐active species. In the propagation phase, HSCs change morphologically into myofibroblast‐like cells characterised by the expression of α‐SMA (Lee & Friedman, 2020). This process can be facilitated by different cell types present in the liver, including infiltrating immune cells (Friedman, 2008; Jakubowska et al., 2020; Karlmark et al., 2009; Kiagiadaki et al., 2018; Thapa et al., 2015), or hepatocytes that release redox‐active species (Friedman, 2008; Wobser et al., 2009), lipid peroxides and cytokines (Lee & Friedman, 2011; Schwabe et al., 2020) (Fig.…”

“…The above traits also well describe the fibroblast type of cells primarily attributed to liver and pancreatic fibrosis: hepatic and pancreatic stellate cells (HSCs and PSCs). HSCs constitute 5–8% of all hepatic cells and form perisinusoidal populations in the space of Disse (Lee & Friedman, 2020; Li et al., 2008; Ye et al., 2021). These cells were first identified in 1952 by Toshio Ito and are often referred to as Ito cells (Ito & Nemoto, 1952).…”

“…For instance, quiescent HSCs store retinoid droplets (vitamin A) and express glial fibrillary acidic protein (GFAP), whereas activated cells do not (Yanguas et al., 2016). Upon activation, HSCs not only become the main source of the fibrous components in the injured liver (Lee & Friedman, 2020), but also perpetuate the fibroinflammatory processes by autocrine or paracrine communication (Li et al., 2008) with hepatocytes (Chung et al., 2016; Dong et al., 2021), Kupffer cells (Cai et al., 2018; Corbett et al., 2015), and liver sinusoidal endothelial cells (Piao et al., 2019; Wu et al., 2021).…”

Metabolic Reprogramming of Liver Fibrosis

“…This new condition is defined as a cluster of fatty liver diseases that are associated with metabolic dysfunction [ 15 ] and it is considered a better criteria to identify patients with significant fibrosis via non-invasive methods [ 16 ]. Other less common diseases that can lead to excessive fibrosis and cirrhosis eventually, include autoimmune hepatitis, hemochromatosis, Wilson’s disease, and primary and secondary biliary cholangitis [ 17 ].…”

“…In contrast, the lifestyle changes that are necessary for the improvement of the metabolic syndrome-associated NAFLD/NASH and obesity, are hard to implement. And unfortunately, the incidence of fibrotic livers due to obesity and metabolic conditions still persists around the globe [ 17 ].…”