Regulating MCP-1 diffusion in affinity hydrogels for enhancing immuno-isolation.
Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward the goal of developing a complete immuno-isolation polymeric barrier, affinity peptide-functionalized PEG hydrogels were developed with the ability to sequester monocyte chemotactic protein 1 (MCP-1), a chemokine known to induce the chemotaxis of monocytes, dendritic cells, and memory T-cells. Affinity peptides capable of sequestering MCP-1 were identified from CCR2 (a G protein-coupled receptor for MCP-1) and incorporated within PEG hydrogels via a thiol-acrylate photopolymerization. The release of encapsulated recombinant MCP-1 from PEG hydrogels is readily tuned by: (1) incorporating affinity peptides within the network; and/or (2) altering the spacer distance between the affinity peptide and the crosslinking site. Furthermore, when pancreatic beta-cells were encapsulated within these novel peptide-functionalized hydrogels, the release of cell-secreted MCP-1 was significantly reduced, demonstrating the potential of this new gel formulation to reduce the host innate immune response to transplanted cells by decreasing the recruitment and activation of host monocytes and other immune cells.
Lin
Chien-Chi
CC
Department of Chemical and Biological Engineering, University of Colorado, 424 UCB, Boulder, CO 80309, USA.
Boyer
Patrick D
PD
Aimetti
Alex A
AA
Anseth
Kristi S
KS
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003432:Cross-Linking Reagents / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003432:Cross-Linking Reagents; D020100:Hydrogels; D009842:Oligopeptides; D011994:Recombinant Proteins; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols