Proliferation and plasticity of human beta cells on physiologically occurring laminin isoforms.
We have previously characterized the molecular composition of human islet basement membranes and shown that human beta cells bind to laminin 511 (LM511) through integrin α3β1 and Lutheran glycoprotein. We have now investigated the impact of physical contact between cultured human beta cells and the laminin isoforms occurring in their natural niche. Human islet preparations derived from 15 donors were used, beta cells and duct cells were purified by magnetic sorting. Overall beta-cell proliferation was low or undetectable. However, in many experiments the only proliferating beta cells were detected in contact with the laminin isoforms that are found in the human islets in vivo (511 and 411). Purified ductal and beta cells underwent epithelial-mesenchymal transition (EMT). LM511 partially blocked this dedifferentiation of purified beta cells, and did not affect purified duct cells. Interactions with the surrounding basement membrane are important for the growth and function of human beta cells. However, only a very limited level of beta-cell proliferation can be induced by exogenous factors. LM511 may be a useful substrate for human beta-cell maintenance in vitro.
Research Programs Unit, Molecular Neurology, Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland.
Meenal
M
Banerjee
Ismo
I
Virtanen
Jaan
J
Palgi
Olle
O
Korsgren
Timo
T
Otonkoski
D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology; D007797:Laminin / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000166:cytology*; D020033:Protein Isoforms / Q000378:metabolism
D007797:Laminin; D020033:Protein Isoforms