Developing defined substrates for stem cell culture and differentiation

Hagbard L., Cameron 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 signalling 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 their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

Functional Diversity of Laminins

Domogatskaya A., Rodin S., Tryggvason K.
Annu Rev Cell Dev Biol., 2012 

This extensive review provides in-depth information on the molecular complexity of laminins and the current knowledge of their diversity and different functional roles. The review gives the reader an understanding of the importance of laminins for different cell- and tissue types in both normal and pathological functioning in mammals at different stages of development and function. 

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 maintains the full integrity and biological activity of laminins and make them the optimal preparations for cell cultivation.

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.

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.

Human embryonic stem cells

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

Short review on 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.

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.G
Cell 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. 

Extracellular Matrix and Integrins in Embryonic Stem Cell Differentiation

Wang H., Luo X. Leighton J.
Biochemistry Insights, 2015

Here, the author summarize 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. 

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.

Expression and biological role of laminin-1

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

Laminin functions in tissue morphogenesis 

Miner J.H. & Yurchenco P.D.
Annu Rev Cell Dev Biol., 2004