Publications

Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.

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  • Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity

    Yao Yao, Zu-Lin Chen, Erin H. Norris, Sidney Strickland. Nature Communications, 2014

    In this article, conditional knockout mice and an acute adenovirus-mediated knockdown model were used to show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown.

  • Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood–brain barrier model

    Louise Delsing, Therése Kallur, Henrik Zetterberg, Ryan Hicks, Jane Synnergren. Fluids Barriers CNS, 2019

    This study shows that astroglia cells differentiated on Biolaminin 521 display an improved phenotype compared to a mouse EHS-extracted laminin L2020 product. Especially, cells differentiated on Biolaminin 521 had a higher secretion of factors important for BBB formation, such as GFAP, S100B, and Angiopoietin-1, than cells differentiated on the laminin extract. In addition, glutamate uptake and the ability to induce the expression of junction proteins in endothelial cells were affected by the culture matrix choice. The study showed differentiation of functional astroglia from three different human induced pluripotent stem cell lines which were used in a blood-brain barrier model.

  • Endothelial Cell Laminin Isoforms, Laminins 8 and 10, Play Decisive Roles in T Cell Recruitment Across the Blood–Brain Barrier in Experimental Autoimmune Encephalomyelitis

    Sixt M., Engelhardt B., Pausch F., Hallmann R., Wendler O., Sorokin L.M. J Cell Biol., 2001

    Laminin-411 and laminin-511 are described as the major laminin isoforms in vascular basement membranes. Their expression was influenced by pro-inflammatory cytokines or angiostatic agents. Inflammatory cuffs occurred exclusively around endothelial basement membranes containing laminin-411, whereas in the presence of laminin-511 no infiltration was detectable. Integrin α6 and β-dystroglycan were prominent in CNS blood vessels, whereas no staining was observed for integrin α3, α7, and β4 subunits. One of the major laminin receptors, integrin α6β1, was localized predominantly on the endothelial cells, where it is likely to mediate interactions with the endothelial cell laminin-411 and -511, whereas astrocyte endfeet appear to utilize a different receptor for interactions with the parenchymal laminins. β-Dystroglycan occurred predominantly on astrocyte endfeet.

  • In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

    Hans C Helms, N Joan Abbott, Malgorzata Burek, Romeo Cecchelli, Pierre-Olivier Couraud, Maria A Deli, Carola Förster, Hans J Galla, Ignacio A Romero, Eric V Shusta, Matthew J Stebbins, Elodie Vandenhaute, Babette Weksler, Birger Brodin. J Cereb Blood Flow Metab, 2016

    This review gives an overview of established in vitro blood-brain barrier models with a focus on their validation regarding a set of well-established blood-brain barrier characteristics. The authors also provide advantages and drawbacks of the different models described.

  • The extracellular matrix protein laminin α2 regulates the maturation and function of the blood-brain barrier

    Michael J Menezes, Freyja K McClenahan, Cindy V Leiton, Azeez Aranmolate, Xiwei Shan, Holly Colognato. J Neurosc, 2014

    In this article, Lama2(-/-) knock-out mice, lacking expression of the laminin α2 subunit of the laminin-211 heterotrimer expressed by astrocytes and pericytes, are shown to have defective blood-brain barrier (BBB ) in which systemically circulated tracer leaks into the brain parenchyma.

  • Astrocytic laminin regulates pericyte differentiation and maintains blood-brain barrier integrity

    Yao Y., Chen Z-L., Norris E.H., Strickland S.Nature comm, 2014

    Here they show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Use conditional knockout mice and an acute adenovirus-mediated knockdown model. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin a2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Loss of astrocytic laminin also decreases aquaporin-4 (AQP4) and tight junction protein expression. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.

  • Tissue distribution of the laminin β1 and β2 chain during embryonic and fetal human development

    Roediger M., Miosge N., Gersdorff N. J Mol Hist., 2010

    Here, the authors investigated the tissue distribution of the laminin b1 and b2 chains on the protein level in various developing embryonic and fetal human organs between gestational weeks 8 and 12. The laminin b1 chain was ubiquitously expressed in the basement membrane zones of the brain, ganglia, blood vessels, liver, kidney, skin, pancreas, intestine, heart and skeletal system. Furthermore, the laminin b2 chain was present in the basement membrane zones of the brain, ganglia, skin, heart, and skeletal system. The findings of this study support and expand upon the theory that these two laminin chains are important during human development. In cartilage, the laminin b1 chain was expressed from gw 10 onwards but not during gw 8 and 9, whereas the detection of the laminin b2 chain was limited to gw 8 and 9. This indicates a developmental switch in the laminin b chain and suggests that the laminin b1 chain does not play a role in human cartilage development until the fetal stage. In human fetal cartilage (gw 17 and 24), a strong pericellular immunohistochemical reaction for laminin 111 was shown. In embryo chick sternum and mouse limb bud, laminin b1 and b2 chains are present in the cytoplasm of chondrocytes.