Laminins as the key to biorelevant cell culture

Cells in the body are almost never alone. Instead, they are surrounded by other cells of its kind, possibly other types of cells and the extracellular matrix. Laminins are the most abundant extracellular proteins closest to the cells and the only proteins that are tissue and cell specific and have an important role in creating this niche. Without this cell niche, cells either go to anioikis and die or try to adapt to the new environment. Therefore, it is crucial to mimic this environment also on plastic cell culture dishes whenever primary cells are cultured in vivo. Otherwise the cells you culture will be out of your control and mutate to something you are not aiming them to be.

“The laminins are transforming cell biology. For millions of years, Nature has developed laminins for cell adhesion and for providing outside-in signals that support phenotypes and cell survival. By using biologically relevant laminins in cell culture matrices one can create proper cell culture niches for better science and clinical translation.”

- Dr. Karl Tryggvasson

The role of extracellular proteins for cells and organs

Tissues contain both cells and extracellular space and the latter consists of a macromolecule network, the extracellular matrix. The extracellular matrix closest to cells is called the basal lamina, which are thin, flexible sheets of specialized matrix composed in large of laminins, entactin, perlecan and collagen IV. It underlies all epithelial sheets and tubes, surrounds individual fat cells, muscle cells and Schwann cells or it can, as in the kidney glomerulus, lie between two individual cell layers.

The role of the basal laminina is more than simple structural and filtering roles. The basal lamina determines cell polarity, influences cell metabolism, organizes proteins in the adjacent plasma membranes, serves as a route for cell migration and promotes cell survival, proliferation and differentiation. The basal lamina and in particular the laminins affect the adjacent cells while at the same time being synthesized and secreted by the very same cells that are associated with it. This is a classic case of inside out and outside in signaling.

The most abundant proteins of the basal lamina are the laminins. Laminins are large glycoproteins with and , and chain and are highly conserved through different species. A simple organism like a Hydra has only one laminin, expressed by its endoderm needed for its ectoderm to produce collagen, together forming the basal lamina between the two cell layers. Through evolution at least 16 identified laminin isoforms with distinct functions are present in the human body. The laminins are the only tissue-specific proteins in the basal lamina. Pluripotent stem cells in the inner cell mass of the blastocysts express laminin-521/511 during embryonic development, skeletal muscle cells are surrounded by laminin-211 and endothelial cells secrete laminin-411/511.

Laminins are mainly thought to mediate their effects through the integrin receptors, but these gigantic proteins can also exert signaling through non-integrin signaling receptors and have shown to have many types of growth factor like properties. As four different laminins can bind to one single integrin receptor and have four different effects on cells, all binding sites of the laminin molecules are important and the whole protein is needed for correct function of the cells.

Professor Karl Tryggvason

Current appointment
2013- Tanato Professor of Diabetes Research, Duke-NUS, Singapore
1994- Professor at Division of Matrix Biology, Karolinska Institutet, Stockholm

Education
1975 MD, University of Oulu, Finland
1977 PhD, Medicine, University of Oulu, Finland

Scientific awards
Icelandic Science Foundation, award
Kaitera Prize, Finland, 1995;
Anders Jahre Prize in Medicine, Oslo, Norway, 1998;
Honorary Professor, Beijing Medical University, 1999;
Homer -Smith Award, American Society of Nephrology, 2000;
Honorary Doctor, University of Iceland, 2001;
Louis -Jeantet Prize in Medicine, Geneva, Switzerland, 2002;
Nils Alwall Prize, International Society of Blood Purification, 2009.

Entrepreneurship
Co-founder, BioStratum Inc, USA, 1994;
Co-founder, NephroGenex Inc, USA, 2007;
Founder, BioLamina AB, Sweden, 2008;
Co -founder, ScaraTech Medical AB, Sweden, 2011.

In Numbers
Invited Speaker to well over 150 international conferences mostly around extracellular matrices and nephrology. Keynote speaker in numerous conferences. Supervised over 42 PhD theses. Over 306 articles, many of them in top-tier publications like Nature, Science and Cell. With over 26 000 citations, one of the most cited scientists at the Karolinska Institute. H-Index 82. 75 review articles and book chapters. Over 30 patents.

 

 

 

The BioLamina foundation

BioLamina is built on a solid scientific foundation and our products are based on research performed by Professor Karl Tryggvason, a world leader in the field of basal lamina (basement membrane) research. He is interested in knowing about the roles of the basal lamina in normal biology and development, its role in human diseases how its proteins such as laminins can find applications. Having cloned most of the human laminin chains, his experience, methods and know-how for production and purification of complex matrix proteins are unparalleled.

This knowledge has been transferred to BioLamina as a direct consequence of requests of scientists around the world to test the various unique human recombinant laminins in their laboratories for answering specific research questions. Due to a large number of requests, it became obvious that it was impossible for a research laboratory to fulfil the human recombinant laminin need of the world’s research community. Therefore, Karl co-founded BioLamina with his son Dr. Kristian Tryggvason in 2008 since he believes these tools are a necessity for biologically relevant cell biology research and applications.

Karl is a native of Iceland, which has formed the basis of his personality. Raised on an island with darkness half of the year and with an average temperature just above freezing both winter and summer makes people stubborn, strong and ready to take on any challenge. Ambitious as he is, he left Iceland already after high school to study medicine. Only a year after he got fascinated about science and started working on his PhD on extracellular proteins.

Medicine was rapidly left behind, when solving scientific problems became his passion. However, the doctor in him has always coupled his scientific questions with medical problems. He has for instance solved the genetic causes of two kidney diseases, one type of muscular dystrophy and a sever skin blistering disease. His studies on the kidney diseases helped him elucidate how the kidney filter functions. Dr. Tryggvason has stayed faithful to the extracellular matrix, but since it affects almost all organs and tissues, he has opened several new fields of research. The reason for this is partly curiosity and serendipity, but also the ability to connect the dots and not discard odd results, but use them as a stepping stone to solving novel problems.

Part of Dr. Tryggvason’s success in science is the ability to see the big picture while at the same time be very detail-oriented. Everything he does, he does well, and demands that of others. With his research group of hungry and talented scientists, he has always been in the forefront of using new techniques that has given him an edge to solving novel problems.