Application of a new cell-adhesive and cell-migatory molecule, laminin-5B, to regenerative medicine

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Laminins are a family of ECM proteins that are localized mainly in basement membranes and regulate various cellular functions such as adhesion, motility, proliferation, apoptosis and differentiation. More than 15 laminin isoforms consisting of different combinations of the three chains have been identified thus far. Among them, laminin-5 (α3A/B, β3, γ2 ; laminin-332), strongly promotes cellular adhesion and migration. Recently we established efficient expression systems of human recombinant laminin-5A (αA, β3, γ2) and laminin-5B (α3B, β3, γ2). In this study, we investigated the possibility to use these laminins for regenerative medicine. We also attempted to establish a system to produce a novel laminin isoform, laminin-6B (α3B, β1, γ1). Main results are as follows. 1) Mesenchymal stem cell (MSC) is thought to be an important cell type in the regenerative medicine, because it can differentiate into osteoblasts, chondrocytes, neural cells, muscle cells and some others. We found that laminin-5A and laminin-5B efficiently stimulated the growth of human MSCs in culture, while suppressing their chondrogenic differentiation. This suggest the possible use of laminin-5A/B as a growth-stimulatory supplement for the efficient in vitro growth of human MSCs. 2) The presence of laminin-6B is predicted, but it has never been identified. We found that this laminin existed in the basement membranes of micro-blood vessels in various human tissues. We also established an efficient expression system of this novel laminin by introducing cDNAs for human laminin α3B, β1, γ1 chains into HEK293 cells. (α3A, β3, γ2). This laminin may play an important role in angiogenesis and maintenance of vascular structures and functions.