Publications
Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
Extracellular Matrix and Integrins in Embryonic Stem Cell Differentiation
Wang H., Luo X. Leighton J.Biochemistry Insights, 2015
Here, the author summarizes the role of the ECM and integrins in the formation of three germ layer progenies. Various ECM–integrin interactions were found, facilitating differentiation toward definitive endoderm, hepatocyte-like cells, pancreatic beta cells, early mesodermal progenitors, cardiomyocytes, neuro-ectoderm lineages, and epidermal cells, such as keratinocytes and melanocytes.
Laminin-332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche
Govaere O. et al. Journal of hepatology, 2015
This study demonstrates that tumor behavior is plastic and depends on the microenvironment of the tumor cell. The authors identified an important role for laminin-332 - more specifically its gamma2-chain - as part of the specialized cancer stem cell niche in maintaining and supporting stemness, e.g. quiescence and chemo-resistance. Laminin-332 not only protects hepatic cancer cells against chemotherapy but even stimulates cell proliferation upon sorafenib exposure. Therefore, monoclonal antibody treatment targeting the gamma2-chain of laminin-332 could provide an innovative therapy for hepatic cancer.
Immunohistochemical Distribution of Laminin-5 γ 2 Chain and its Developmental Change in Human Embryonic and Foetal Tissues
Lu W., Miyazaki K., Mizushima H., Nemoto N.
Here, immunohistochemical distribution of laminin γ2 chain, a subunit of the basement membrane protein laminin 332, was examined in 19 cases of human embryos and foetuses ranging from 4 to 25 weeks of gestation. Laminin γ2 was first detected in the basement membranes underlying ectodermal epithelial tissues, such as the skin and tooth, as early as 5–6 weeks of gestation. Between 6–7 and 12–13 weeks, laminin γ2 was detected in the basement membranes of various endodermal epithelial tissues, such as the bronchus, oesophagus, stomach, intestines, urinary bladder, gallbladder, and hepatopancreatic duct. The deposition of laminin γ2 in the basement membrane was associated with the process of morphogenesis. In the small intestine, laminin γ2 first appeared in the basement membrane of the primitive short villi, and its level gradually increased in the villus region but decreased in the cryptic region during the maturation of the organ. In addition, non-basement membrane immunoreactivity for laminin γ2 was detected in some mesoderm-derived tissues, such as the cartilage and skeletal and smooth muscle fibers. These results suggest a common role of laminin 332 and some specific roles of its γ2 chain in the morphogenesis of human tissues.
Immunohistochemical Distribution of Laminin-5 γ 2 Chain and its Developmental Change in Human Embryonic and Foetal Tissues
Lu W., Miyazaki K., Mizushima H., Nemoto N.The Histochemical Journal, 2001
Here, immunohistochemical distribution of laminin γ2 chain, a subunit of the basement membrane protein laminin 332, was examined in 19 cases of human embryos and fetuses ranging from 4 to 25 weeks of gestation. Laminin γ2 was first detected in the basement membranes underlying ectodermal epithelial tissues, such as the skin and tooth, as early as 5–6 weeks of gestation. Between 6–7 and 12–13 weeks, laminin γ2 was detected in the basement membranes of various endodermal epithelial tissues, such as the bronchus, oesophagus, stomach, intestines, urinary bladder, gallbladder, and hepatopancreatic duct. The deposition of laminin γ2 in the basement membrane was associated with the process of morphogenesis. In the small intestine, laminin γ2 first appeared in the basement membrane of the primitive short villi, and its level gradually increased in the villus region but decreased in the cryptic region during the maturation of the organ. In addition, non-basement membrane immunoreactivity for laminin γ2 was detected in some mesoderm-derived tissues, such as the cartilage and skeletal and smooth muscle fibers. These results suggest a common role of laminin 332 and some specific roles of its γ2 chain in the morphogenesis of human tissues.
Imaging-Based Screen Identifies Laminin 411 as a Physiologically Relevant Niche Factor with Importance for i-Hep Applications
Ong J., Paola Serra M., Segal J., Cujba A.-M., Seng Ng S., Butler R., Millar V., Hatch S., Zimri S., Koike H., Chan K., Bonham A., Walk M., Voss T., Heaton N., Mitry R., Dhawan A., Ebner D., Danovi D., Nakauchi H., Rashid S.T.Stem Cell Reports, 2018
Here, the authors show that extracellular niche factors likely play a critical role in bridging this gap in functional differences between hepatocytes derived from induced pluripotent stem cells (i-Heps) and primary cells. They defined a profile of healthy, freshly isolated primary hepatocytes (Hepatocyte Likeness Index; HLI) that cells of interest can be compared against for high-throughput screening. They applied this platform to screen hepatocyte niche factors for their ability to drive i-Heps closer to that target and validated their findings in a pharma-like screening environment. The HLI was applied in a targeted screen of extracellular niche factors to identify substrates driving i-Heps closer to the standard. Results from the screen performed highlighted the important role played by laminins where laminin 411 was identified as a key niche protein. Laminin 411 is a component of the hepatic niche. Laminin 411 advanced i-Heps toward functional significance and prolonged survival of hepatic progenitor cells, contributing to better i-Hep-based drug-screening applications. This paper underscores the importance of combining substrates, soluble factors, and HCA when developing iPSC applications.
Characterization of a stereotypical cellular and extracellular adult liver progenitor cell niche in rodents and diseased human liver
Lorenzini S., Bird T.G., Boulter L., Bellamy C., Samuel K., Aucott R., Clayton E., Andreone P., Bernardi M., Golding M., Alison M.R., Iredale J.P., Forbes S.J.Gut, 2010
In this article, the composition and formation of stem progenitor cell niches were examined. The progenitor cell response in liver injury is intimately surrounded by myofibroblasts and macrophages, and to a lesser extent by endothelial cells. Hepatic progenitor cells are not of bone marrow origin; however, bone marrow-derived cells associate intimately with these cells and are macrophages. Laminin always surrounds the progenitor cells. In vitro studies showed that laminin aids the maintenance of progenitor and biliary cell phenotype and promotes their gene expression (Dlk1, Aquaporin 1, gammaGT) while inhibiting hepatocyte differentiation and gene expression (CEPB/alpha). During liver damage in rodents and humans, a stereotypical cellular and laminin niche forms around hepatic progenitor cells. Laminin helps the maintenance of undifferentiated progenitor cells. The niche links the intrahepatic progenitor cells with bone marrow-derived cells and links tissue damage with progenitor cell-mediated tissue repair.
Laminin 411 and 511 promote the cholangiocyte differentiation of human induced pluripotent stem cells
Takayama K., Mitani S., Nagamoto Y., Sakurai F., Tachibana M., Taniguchi Y., Sekiguchi K., Mizuguchi H. Biochem Biophys Res Commun. 2016
Here the authors searched for a suitable extracellular matrix to promote cholangiocyte differentiation from human iPS cells and found that both laminin 411 and laminin 511 were suitable for this purpose. Differentiated human iPSC to cholangiocyte-like cells via hepatoblasts-like cells (derived according to previous papers). The hepatoblast-like cells were mixed in a collagen gel and plated and for cholangiocyte differentiation, laminin was added to the medium. The gene expression levels of the cholangiocyte markers, aquaporin 1 (AQP1), SRY-box 9 (SOX9), cystic fibrosis transmembrane conductance regulator (CFTR), G protein-coupled bile acid receptor 1 (GPBAR1), Jagged 1 (JAG1), secretin receptor (SCTR), and g-glutamyl transferase (GGT1) were increased by using laminin 411 or laminin 511 as a matrix. In addition, the percentage of AQP1-positive cells was increased from 61.8% to 92.5% by using laminin 411 or laminin 511. Furthermore, the diameter and number of cysts consisted of cholangiocyte-like cells were increased when using either matrix.