Publications
Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
Publication: Biosilk with laminin-521 for hPSC neural differentiation in 3D network
Åstrand et al. 2020 Biomaterials Science
This article describes the use of a recombinant spider silk protein functionalized with a cell binding motif from fibronectin in combination with a human recombinant laminin 521 (LN-521) to create a fully defined stem cell niche in 3D. The results show that hPSCs integrated into the foam develop into neural progenitors and that they stay viable during long-term differentiations. The culture system also supports morphogenesis mimicking the human brain development and can serve as base for engineering of hPSC-derived neural tissue. The article describes the 3D culture matrix sold under the name Biosilk®.
Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons
Nolbrant S., Giacomoni J., Hoban D.B, Bruzelius A., Birtele M., Chandler-Militello D., Pereira M., Rylander Ottosson D., Goldman S.A., Parmar M. Stem Cell Reports, 2020
Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors using human cells has been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, the authors provide evidence that hGPCs isolated from both the human fetal brain and differentiated from hESCs can be successfully reprogrammed into functional iNs, including induced DA neurons (iDANs). They also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, they have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson’s disease.
Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons
Li-Yang Chiang, Kate Poole, Beatriz E Oliveira, Neuza Duarte, Yinth Andrea Bernal Sierra, Leena Bruckner-Tuderman, Manuel Koch, Jing Hu, Gary R Lewin. Nature Neuroscience, 2011
The authors found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Laminin-332 could locally control sensory axon branching behavior, and the loss of laminin-332 in humans led to increased sensory terminal branching and may lead to a de-repression of mechanosensitive currents.
Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
Tanja Hyvärinen, Anu Hyysalo, Fikret Emre Kapucu, Laura Aarnos, Andrey Vinogradov, Stephen J Eglen, Laura Ylä-Outinen, Susanna Narkilahti. Sci Rep, 2019
In this article, differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate is reported. They assessed compared the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures using microelectrode array (MEA) measurements. The authors conclude that hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, and they could be applied as a human-specific model for pharmacological studies and modeling network dysfunctions.
Efficiently Specified Ventral Midbrain Dopamine Neurons from Human Pluripotent Stem Cells Under Xeno-Free Conditions Restore Motor Deficits in Parkinsonian Rodents
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish. Stem Cells Transl Med, 2017
The authors describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs for use in animal models of Parkinson's disease. This protocol, utilizing Biolaminin 521 as a component, consistently increases both the yield and proportion of vmDA neural progenitors and neurons that display classical vmDA metabolic and electrophysiological properties. These findings may help in translation of hPSC-derived neurons into the clinic.
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.
Functionality of endothelial cells and pericytes from human pluripotent stem cells demonstrated in cultured vascular plexus and zebrafish xenografts
Valeria V Orlova, Yvette Drabsch, Christian Freund, Sandra Petrus-Reurer, Francijna E van den Hil, Suchitra Muenthaisong, Peter Ten Dijke, Christine L Mummery. Arterioscler Thromb Vasc Biol, 2014
This article describes simultaneous derivation of endothelial cells and pericytes from hiPSCs of different tissue origin.
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.
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 adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with Laminin-211
Petersen SC. et al.
In the peripheral nervous system, Schwann cell (SC) myelination requires the adhesion G protein-coupled receptor GPR126, which undergoes autoproteolytic cleavage into an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). The authors noticed biphasic roles of GPR126 which were governed by interactions with Laminin-211 - a novel ligand for GPR126 that modulates receptor signaling via a tethered agonist. The work suggests a model in which Laminin-211 mediates GPR126-induced cAMP levels to control early and late stages of SC development.