Mesenchymal Stromal Cells for Sphincter Regeneration: Role of Laminin Isoforms upon Myogenic Differentiation

In the sphincter tissue (smooth muscle), a strong expression of the isoforms laminin-211/221, laminin-411/421 and laminin-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms laminin-411 and laminin-511, but not laminin-211. Even after myogenic differentiation, laminin-211 can hardly be detected. All laminin isoforms tested (-211, -411, -511 and -521) showed significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of laminin-521, they had no influence on the proliferation of MSCs cultivated in a myogenic medium. The strongest cellular adhesion of MSCs was to laminin-511 and laminin-521, whereas laminin-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with laminin-211, but it did not affect the interaction with laminin-511 and laminin-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells.