title: Cell-cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing beta-cell function.
abstract: A biomimetic hydrogel platform was designed to signal encapsulated cells using immobilized cell-cell communication cues, with a focus on enhancing the survival and function of encapsulated pancreatic β-cells to treat type 1 diabetes. When MIN6 cells, a pancreatic β-cell line, were encapsulated in poly(ethylene glycol) (PEG) hydrogels, their survival and glucose responsiveness to insulin were highly dependent on the cell-packing density. A minimum packing density of 10(7) cells/mL was necessary to maintain the survival of encapsulated β-cells without the addition of material functionalities (e.g., cell adhesion ligands). While single cell suspensions can improve diffusion-limited mass transfer, direct cell-cell interactions are limited. Thus, thiolated EphA5-Fc receptor and ephrinA5-Fc ligand were conjugated into PEG hydrogels via a thiol-acrylate photopolymerization to render an otherwise inert PEG hydrogel bioactive. The biomimetic hydrogels presented here can provide crucial cell-cell communication signals for dispersed β-cells and improve their survival and proliferation. Together with the cell-adhesive peptide RGDS, the immobilized fusion proteins (EphA5-Fc and ephrinA5-Fc) synergistically increased the survival of both MIN6 β-cells and dissociated islet cells, both at a very low cell-packing density (< 2 × 10(6) cells/mL). This unique gel platform demonstrates new strategies for tailoring biomimetic environments to enhance the encapsulation of cells that require cell-cell contact to survive and function.
authors.affiliation: Department of Biomedical Engineering, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, USA. lincc@iupui.edu
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002470:Cell Survival; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000628:therapy; D036386:Ephrin-A5 / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D036123:Receptor, EphA5 / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D036386:Ephrin-A5; D020100:Hydrogels; D007141:Immunoglobulin Fc Fragments; D007328:Insulin; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D011092:Polyethylene Glycols; C046617:arginyl-glycyl-aspartyl-serine; D036123:Receptor, EphA5; D005947:Glucose