Functional diversity of laminins

The physical, topological, and biochemical expression of the different laminin (LN) isoforms in the BM is heterogeneous which results in extremely diverse functions, such as tissue structure and permeability, cell polarity, metabolism, survival, migration, proliferation and differentiation. Without the right combination of laminin isoforms cells and tissues becomes dysfunctional (Domogatskaya et al., 2012; Miner & Yurchenco, 2004). While epithelial cells need LN-332 together with LN-511/521, muscle and nerve cells need LN-211, LN-221 and LN-511/521, and endothelial cells require LN-411 combined with LN-511 for proper function (Domogatskaya et al. 2008, Nikolova et al. 2006, Rodin et al. 2010). Particularly those laminin isoforms possessing the γ1 subunit are involved in many biological activities (Yurchenco 2015). By culturing cells on the laminin isoform in vitro that they normally adhere to in vivo, the biorelevant niche is partly recapitulated by the medium and the matrix. 


Laminins are important for embryogenesis and the isoform expression changes during development. In the developing embryo, laminins containing the alpha-1 and alpha-5 subunits are the first extracellular proteins to be expressed. The LN-111 is mostly expressed in Reichert’s membrane which supports the outer, extra-embryonic layer of trophoblasts. Contrary, LN-521 and LN-511 are expressed around the stem cells in the inner cell mass and support survival and self-renewal of the pluripotent stem cells (Domogatskaya et al., 2012; Ekblom et al., 2003; Miner & Yurchenco, 2004). After birth, the alpha-5 laminins represent the most commonly expressed laminins (Miner et al., 1995) whereas the distribution of LN-111 is restricted to only a few tissues, such as brain and kidney (Yurchenco, 2015).


Read more about different applications for our laminins.

RPE and photoreceptor cell culture
Culture retinal pigmented epithelial (RPE) cells, photoreceptors and other retinal cells on the laminins expressed in Bruch´s membrane and the neuroepithelium.
   
Maintaining endothelial cells in culture
Endothelial cells and progenitors can be maintained for months without signs of de-differentiation on laminins.
   
Functional hepatocyte culture
The liver contains several different laminin isoforms and experiments show that laminins promote attachment, purification and differentiation of hepatoblasts and mature hepatocytes in culture.
   
Skeletal muscle cells
The most abundant laminin isoform in the basement membrane of adult skeletal muscle is laminin-211 and mutations in the gene encoding laminin a2 chain causes congenital muscular dystrophy.
   
Pancreatic cells and islets
Expansion of primary pancreatic islets on specific laminins results in proliferation of beta cells, delta cells, alpha cells and endothelial cells along with maintained insulin-production.
   
Human pluripotent stem cell culture
Derivation, reprogramming, expansion and differentiation of human PSCs in chemically defined, feeder and xeno-free conditions with reliable results is easy with the correct laminin isoform.
   
Cell culture of neurons and neural stem cells
Culture dopaminergic neurons, neural stem cells, motor neurons and other neural cells on their respective laminins to increase adhesion, neurite outgrowth, maturity and functionality.
   
Clonal pluripotent stem cell culture
Generation of stem cell clones by seeding one single PSC in an individual well is possible when using a biorelevant combination of matrix proteins of which one is laminin. It is perfect to increase survival at clonal densities for genome editing and after sorting.
   
Culture beating cardiomyocytes
Chemically defined generation of human cardiomyocytes from PSCs is improved with cardiac laminins that increase the yield, adhesion and maturation of cardiomyocytes.
   
Epithelium and keratinocyte culture
In epithelial basement membranes laminin-332 is enriched and upregulated during wound healing affecting keratinocyte migration, proliferation and skin tissue remodeling.
   
Kidney cell culture
In the kidney glomerular basement membrane and for podocytes, one specific laminin is responsible for the glomerular capillary loop structure. 



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REFERENCES

  • Functional diversity of laminins. Domogatskaya et al. Annu Rev Cell Dev Biol., 2012
  • Laminin-511 but not -332, -111, or -411 enables mouse embryonic stem cell self-renewal in vitro. Domogatskaya et al. Stem Cells, 2008
  • Expression and biological role of laminin-1. Ekblom et al. Matrix Biol., 2003
  • Trophoblast-specific expression and function of the integrin α7 subunit in the peri-implantation mouse embryo. Klaffky et al. Dev. Biol., 2001
  • Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Miner et al. Development, 2004
  • Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues. Miner et al. Journal of Biological Chemistry, 1995
  • Laminin functions in tissue morphogenesis. Miner & Yurchenco. Annu Rev Cell Dev Biol., 2004
  • The vascular basement membrane: a niche for insulin gene expression and βcell proliferation. Nikolova et al. Dev. Cell, 2006
  • Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511. Rodin et al. Nat. Biotechnol., 2010
  • Integrating Activities of Laminins that Drive Basement Membrane Assembly and Function. Yurchenco. Current Topics in Membranes, 2015