Laminins — extracellular modulators of stem cell and cell lineage behavior

The laminins are a family of large basement membrane proteins that influence cell differentiation, adhesion, migration, and phenotype stability. They are heterotrimeric glycoproteins that exist in at least 16 different chain combinations of α, β and γ chains. The different isoforms have highly cell and tissue specific locations and specific biological roles in respective tissues. We have produced nine of those isoforms as human recombinant proteins and initiated studies on their effects on various types of cultured cells. We have previously shown that laminin-511 (α5:β1:γ1), that is expressed by pluripotent human stem (hES) cells, alone can support long-term self-renewal of hES and iPS (hES/iPS) cells in a xeno-free cell culture environment (Rodin et al., 2010, Nat Biotechnol). However, this laminin did not permit survival of the cells after replating from single cell suspension. In contrast, another recombinant human laminin-521, also expressed by cultured pluripotent hES cells and which is part of the natural niche of cells of the blastocyst inner cell mass, did allow both derivation of single hES cells and expansion from single cell suspension. The hES cells can be propagated as homogenous monolayers on laminin-521 in a completely defined, feeder-free and xeno-free cell culture system. The effects of laminins 511 and 521 on pluripotent stem cells are mediated by interaction with integrin α6β1 via the PI3K/Akt signaling pathway. Laminin-based cell culture systems for hES and hiPS cells have made culturing of such cells easy and they can greatly facilitate the generation of stem cell derived differentiated cells for cell therapy purposes. Other laminin isoforms exert various effects, including differentiation and phenotype stabilization, on other cell types, and those properties will be discussed briefly. Plenary Lectures