Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity screening of pharmaceuticals

Investigating the potential immune role of fish NCAMs: Molecular cloning and expression analysis in mandarin fish

“…In mammals, the hemophilic interactions mediated via NCAM2 expressed by NK cells are important for cellular recognition in relation to immune responses [3]. On the other side, NCAM2, as one of the markers of hepatic progenitor cells, is also expressed in acute and chronic damaged livers [8]. Thus, though with low constitutive expression, mfNCAM2 up-regulated only in liver and responsed more quickly to viral rather than bacterial analogue might result from the response of either liver NK cells or hepatic progenitor cells to stimulation.…”

“…CD56, as the only isoform expressed on immune cells, has been found distributed in a variety of cells including neurons, astrocytes, Schwann cells, natural killer (NK) cells, and a subset of T (natural killer T, NKT) cells [6]. Meanwhile, mammalian NCAM2 is primarily expressed in the brain [3]; and non-neural NCAM2 expression has been found regulated by the cytokines Abbreviations: ARE, AU-rich element; CCCL, clonal cytotoxic cell line; dpi, day post injection; DC, dendritic cell; FBA, F-box associated region; FNIII, fibronectin type III; hpi, hour post injection; Ig, immunoglobulin; IHC, immunohistochemistry; IHIC, intrahepatic immune cells; ISH, in situ hybridization; NCAM, neural cell adhesion molecule; NCC, nonspecific cytotoxic cell; NK cell, natural killer cell; NKT cell, natural killer T cell; PBL, peripheral blood leukocyte; qPCR, quantitative realtime PCR; UTR, untranslated region; VASE, variable alternative spliced exon.essential for NK cell survival and differentiation [7], and also associated with progenitor cell [8] and cancer cell [9].…”

Innovation for hepatotoxicity in vitro research models: A review

“…iPSCs and stem-cell-derived hepatocytes, such as human embryonic stem-cell-derived (ESCs), human skin-derived precursors (hSKPs) and human fetal hepatic progenitor cells (hFHPCs) are emerging as important potential sources of unlimited numbers of hepatocytes (Guguen- Guillouzo, Corlu, & Guillouzo, 2010;Kim et al, 2017;Rodrigues et al, 2014;Si-Tayeb et al, 2010;Takahashi et al, 2007;Zhang et al, 2012). iPSCs reprogrammed from somatic cells using transcription factors have been induced to differentiate into many types of functional cells, such as hepatocytes, neurons, cardiomyocytes and mesenchymal stem cells (Fine et al, 2013;Hu et al, 2010;Pagliuca et al, 2014).…”

“…hSKPs and hFHPCs can efficiently differentiate into HLCs in vitro. hSKP/HLCs and hFHPCs/HLCs acquire highly differentiated hepatic functions, and can express hepatic progenitor cell markers and adult hepatocyte marker gene expression, such as albumin, as well as key biotransformation enzymes and influx and efflux drug transporters (Rodrigues et al, 2014;Zhang et al, 2012).…”

“…ESCs/HLCs can investigate the hepatotoxicity of drugs, such as acetaminophen and thiazolidinediones, and predict the hepatotoxicity of Chinese herbal medicines and show their toxicity patterns (Duan et al, 2010;Kim et al, 2017). Rodrigues et al investigated the steatosis-inducing effects of sodium valproate using hSKP/HPCs (Rodrigues et al, 2014). Exposure of hSKPs/HPCs to sub-cytotoxic concentrations of this reference steatogenic compound showed increased intracellular accumulation of lipid droplets and the modulation of key factors involved in lipid metabolism (Rodrigues et al, 2016).…”