Hydrogel encapsulation environments functionalized with extracellular matrix interactions increase islet insulin secretion.
The individual and synergistic effects of extracellular matrix interactions on isolated islet function in culture were investigated within a three-dimensional poly(ethylene glycol) (PEG) hydrogel encapsulation environment. First, we observed similar glucose-stimulated insulin secretion from unencapsulated murine islets and islets photoencapsulated in PEG gels. Then islets were encapsulated in gels containing the basement membrane proteins collagen type IV and laminin, individually and in combination, at a total protein concentration of 100 microg/ml, and islet insulin secretion in response to high glucose was measured over time. Specific laminin interactions were investigated via islet encapsulation with adhesive peptide sequences found in laminin as well as via functional blocking of cell surface receptors known to bind laminin. Over 32 days, islet interactions with collagen type IV and laminin localized within the three-dimensional extracellular environment contributed to two-fold and four-fold increases in insulin secretion, respectively, relative to islets encapsulated without matrix proteins. Hydrogel compositions containing both matrix proteins and >75% laminin further increased islet insulin secretion to approximately six-fold that of islets encapsulated in the absence of matrix proteins. Encapsulation with the peptide sequence IKVAV resulted in increased islet insulin secretion, but not to the extent observed in the presence of whole laminin. Increased insulin secretion in the presence of laminin was eliminated when islets were exposed to functionally blocking anti-alpha6 integrin antibody prior to islet encapsulation with laminin. Our results demonstrate the potential of specific matrix interactions within an islet encapsulation microenvironment to promote encapsulated islet function.
Weber
Laney M
LM
Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309-0424, USA.
Anseth
Kristi S
KS
D000818:Animals; D002214:Capsules; D005109:Extracellular Matrix / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface / Q000378:metabolism
D002214:Capsules; D007328:Insulin; D007797:Laminin; D011956:Receptors, Cell Surface; C052131:extracellular matrix receptor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005947:Glucose
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