Publications

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

  • Area of interest

  • Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks

    Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks

    Sorkioa A., Kochb L., Koivusaloa L., Deiwickb A., Miettinena S., Chichkovb B., Skottman H.
    Biomaterials, 2018

    In this study, the authors produced 3D cornea-mimicking tissues using human stem cells and laser-assisted bioprinting (LaBP). Human embryonic stem cell-derived limbal epithelial stem cells (hESC-LESC) were used as a cell source for printing epithelium-mimicking structures, whereas human adipose tissue-derived stem cells (hASCs) were used for constructing layered stroma-mimicking structures. The authors used two previously established LaBP setups based on laser-induced forward transfer, with different laser wavelengths and appropriate absorption layers. Recombinant human laminin and human-sourced collagen I served as the bases for the functional bioinks. For hESC-LESCs, bioink containing human recombinant laminin-521 was chosen, as laminin is a major component in LESC basement membrane in the native cornea. Three different types of corneal structures was printed: stratified corneal epithelium using hESC-LESCs, lamellar corneal stroma using alternating acellular layers of bioink and layers with hASCs, and finally structures with both a stromal and epithelial part. The printed constructs were evaluated for their microstructure, cell viability and proliferation, and key protein expression. The 3D printed stromal constructs were also implanted into porcine corneal organ cultures. Both cell types maintained good viability after printing. Laser-printed hESC-LESCs showed epithelial cell morphology, expression of Ki67 proliferation marker and co-expression of corneal progenitor markers p63α and p40. Importantly, the printed hESC-LESCs formed a stratified epithelium with apical expression of CK3 and basal expression of the progenitor markers. The structure of the 3D bioprinted stroma demonstrated that the hASCs had organized horizontally as in the native corneal stroma and showed positive labeling for collagen I. After 7 days in porcine organ cultures, the 3D bioprinted stromal structures attached to the host tissue with signs of hASCs migration from the printed structure. This is the first study to demonstrate the feasibility of 3D LaBP for corneal applications using human stem cells and the successful fabrication of layered 3D bioprinted tissues mimicking the structure of the native corneal tissue.

  • Expression and biological role of laminin-1

    Ekblom P., Lonai P., Talts J.F'
    Matrix Biol., 2003

  • Engineered Human Stem Cell Microenvironment

    Jordahl J.H., Villa-Diaz L., Krebsbach P.H., Lahann J.Stem Cells and Nanotechnologies, 2016

    Review of engineered stem cell niches. Laminin (from various sources) is throughout the paper pointed out is the single most important factor for culturing both hPSCs but also many other stem cells.

  • 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. 

  • Human Pluripotent Stem Cell Culture: Considerations for Maintenance, Expansion, and Therapeutics

    Kevin G. Chen K.G., Mallon B.S., McKay R.D.G., Robey P.GCell stem cell, 2014

    In this review, the authors look at different large-scale hPSC culture growth components by comparing cell culture methods (matrices, media, etc.) and identifying the advantage and disadvantages and pitfalls associated with each one. Since laminin-521 was not available when the review was written, they only mention laminin-511 where the cells are seeded as clumps (Rodin et al 2010). The only disadvantage mentioned regarding laminin-511 is that the use of laminin for maintenance and expansion will be to thigh due to the price of the laminins. 

  • Human embryonic stem cells

    Damdimopoulou P., Rodin S., Stenfelt S., Antonsson L., and Tryggvason K., Hovatta O. Best Practice & Research Clinical Obstetrics & Gynaecology, 2015

    A short review on the establishment of hESC lines on LN-521. Authors state that they easily can establish and expand hESC lines in fully chemically defined animal substance-free conditions. hESC lines can be derived from single biopsied cells of embryos that need not be destroyed during the process. The genetic stability and differentiation capacity can be studied. These cell lines can today be safely expanded almost without limitations.

  • Molecular Basis of Laminin–Integrin Interactions

    Yamada M. and Sekiguchi K. Current Topics in Membranes, 2015

    Review about the molecular basis and physiological relevance of specific interactions between laminins and integrins. Describe the mechanisms underlying laminin action through integrins.

  • Animal Substance-Free Human Embryonic Stem Cells Aiming at Clinical Applications

    Hovatta O., Rodin S., Antonsson L., and Tryggvason K. Stem Cells Transl Med,. 2014

    In this concise review, the authors describe that it is now feasible to establish clinical-grade hESC lines in animal substance-free chemically defined conditions with the Laminin-521 matrix. They discuss recent developments and the progress to now being able to generate genetically stable hESC lines even from single biopsied blastomeres without destroying the embryo.

  • Characterization of commercial laminin preparations from human placenta in comparison to recombinant laminin-211, -411, and -511

    Wondimu Z., Gorfu G., Kawataki T., Smirnov S., Yurchenco P., Tryggvason K., Patarroyo M.Matrix Biol., 2006

    This paper compares purified laminins to human recombinant laminins. The major findings are that laminin preparations that have been purified from different tissues (in contrast to recombinantly produced laminins) consist of fragmented proteins, different laminin isoforms and unwanted, contaminating fibronectin. In addition to undefined and heterogenous preparations, they show large batch-to-batch variations. In conclusion, only human recombinant laminins maintain the full integrity and biological activity of laminins and make them the optimal preparations for cell cultivation.

  • Developing defined substrates for stem cell culture and differentiation

    Hagbard L.,bCameron K., August P., Penton C., Parmar M., Hay D.C., Kallur T.Phil. Trans. R. Soc. B, 2018

    In this review article, we revisit the basics of the extracellular matrix and explore the important role of the cell-matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification. Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signaling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune theirs in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. This article is part of the themed issue ‘Designer human tissue: coming to a lab near you’.