Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
Neuronal Replacement as a Tool for Basal Ganglia Circuitry Repair: 40 Years in Perspective
Björklund A. and Parmar M. Front. Cell. Neurosci., 2020
In this review article, the authors give an overview of past and current efforts to restore damaged connectivity in the adult mammalian brain using implants of fetal neuroblasts or stem cell-derived neuronal precursors. Focus on strategies aimed to repair damaged basal ganglia circuitry induced by lesions that mimic the pathology seen in humans affected by Parkinson’s or Huntington’s disease.
Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease
Tiklová K., Nolbrant S., Fiorenzano A., Björklund Å.K., Sharma Y., Heuer A., Gillberg L., Hoban D.B., Cardoso T., Adler A.F., Birtele M., Lundén-Miguel H., Volakakis N., Kirkeby A., Perlmann T., Parmar M.
Cell replacement for the treatment of Parkinsonʼs disease (PD) can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, the authors use single-cell RNA sequencing (scRNA-seq) combined with histological analyses to characterize intracerebral grafts from ventral midbrain (VM)-patterned human embryonic stem cells (hESCs) and VM fetal tissue after long-term survival and functional maturation in a preclinical rat model of PD. Neurons and astrocytes were shown to be major components in both fetal and stem cell-derived grafts but oligodendrocytes are only detected in grafts of fetal tissue. On the other hand, a cell type closely resembling a class of newly identified perivascular-like cells is identified as a previously unknown component of hESC-derived grafts.
An Optimized Protocol for the Generation of Midbrain Dopamine Neurons under Defined Conditions
Gantner C.W., Cota-Coronado A., Thomp L.H.STAR Protocols, 2020
Here, the authors describe a xeno-free, feeder-free, and chemically defined protocol for the generation of ventral midbrain dopaminergic (vmDA) progenitors from human pluripotent stem cells (hPSCs). This simple-to-follow protocol results in high yields of cryopreservable dopamine neurons across multiple hPSC lines. Wnt signaling is the critical component of the differentiation and can be finely adjusted in a line-dependent manner to enhance the production of dopamine neurons for the purposes of transplantation, studying development and homeostasis, disease modeling, drug discovery, and drug development.
β1 Integrin Maintains Integrity of the Embryonic Neocortical Stem Cell Niche
Loulier et al.
Hippocampal neurons: Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/plasmin protease cascade during excitotoxic injury
Indyk et al.
Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal
Fietz et al.
Laminin enhances the growth of human neural stem cells in defined culture media
Hall et al.
BMC Neuroscience, 2008
Adult SVZ Stem Cells Lie in a Vascular Niche: A Quantitative Analysis of Niche Cell-Cell Interactions
Shen Q., Wang Y., Kokovay E., Lin G., Chuang S-M. Goderie S.K., Roysam B., Temple S. Cell Stem Cell, 2008
Here, they examine the relationship of adult SVZ NSC lineage cells to blood vessels using confocal imaging of SVZ whole mounts in which the normal 3D relationships of cells are preserved. Neural stem cells (NSCs) in the adult subventricular zone (SVZ) lie close to blood vessels in a vascular-derived laminin-rich niche. Cells expressing stem cell markers, including GFAP, and proliferation markers are closely apposed to the laminin-containing extracellular matrix (ECM) surrounding vascular endothelial cells. Adult SVZ progenitor cells express the laminin receptor a6B1 integrin, and blocking this inhibits their adhesion to endothelial cells, altering their position and proliferation in vivo.
Laminin and growth factor receptor activation stimulates differential growth responses in subpopulations of adult DRG neurons
Tucker B.A., Rahimtula M., Mearow K.M.European Journal of Neuroscience, 2006
Here they show laminin-induced neurite outgrowth and its relation to three known DRG neuronal types. They also show PI3K pathway is responsible. They also discuss this in the light of possible therapeutic targets. The study is limited in that that they only use invitrogen laminin (purified laminin-111) and isoform-specific effects cannot be seen, but they come to a number of highly interesting conclusions: 1) The current findings provide strong support for the use of the ECM molecule laminin in conjunction with NGF and GDNF in order to stimulate optimal levels of axon growth from all populations of regenerating sensory neurons. 2) identified intracellular signaling components that provide potential therapeutic targets when attempting to stimulate the regeneration of peripheral axons. Pharmacological alterations of the PI 3-K/Akt pathway resulting in activation of either PI 3-K or Akt could be beneficial. 3) Laminin-induced neurite growth occurs in the absence of added trophic factors only in heavy-chain neurofilament-positive and calcitonin gene-related peptide-positive DRG neurons [nerve growth factor (NGF)-responsive population]. In contrast, laminin alone is not sufficient to stimulate significant neurite growth from lectin Griffonia simplicifolia IB4-positive neurons (IB4+ve), although it is still required to elicit a growth response from these cells in the presence of glial-derived neurotrophic factor.
Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer's disease
Zekonyte J., Sakai K., Nicoll J.A.R., Weller R.O., Carare R.O.Biochimica et Biophysica Acta, 2015
Accumulation of amyloid-β (Aβ) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of Aβ from the brain with age and Alzheimer's disease. A major pathway for elimination of Aβ and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. Since Aβ40 is the predominant type of Aβ found in cerebral amyloid angiopathy, in the present study we tested the hypothesis that interactions of Aβ40 with protein components of cerebral vascular basement membranes, such as laminin, are stronger in the presence of ApoE3 than in the presence of ApoE4. Proteins (LN-511, ApoE3, or ApoE4) were immobilized on AFM probes using the amine–amine-reactive linker aldehyde–PEG–NHS. Force-spectroscopy experiments were performed to study the reciprocal influence of different isoforms of ApoE and Aβ on their binding interactions with laminin-511. The results show that apolipoprotein E co-localizes with Aβ in basement membrane drainage pathways in the walls of arteries. Moreover, all AFM measurements demonstrate that Aβ + ApoE3 complex has a stronger binding to laminin-511 than Aβ + ApoE4. These results suggest that perivascular elimination of ApoE4/Aβ complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer's disease. Therapeutic correction for ApoE4/Aβ/laminin interactions may increase the efficiency of the elimination of Aβ in the prevention of Alzheimer's disease.