Mesenchymal stem cells and ligand incorporation in biomimetic poly(ethylene glycol) hydrogels significantly improve insulin secretion from pancreatic islets.
The main goal of this study was to investigate pancreatic islet function with mesenchymal stem cells (MSCs) in a ligand-functionalized poly(ethylene glycol) (PEG) hydrogel for the treatment of type 1 diabetes (T1D). Rat bone marrow-derived MSCs (rBM-MSCs) were encapsulated within synthetic PEG hydrogel, and cell viability and apoptosis within this 3D environment was examined in detail. ATP content and caspase-3 activity of encapsulated MSCs showed that fibronectin-derived RGDS, laminin-derived IKVAV and/or insulinotropic glucagon-like peptide (GLP-1) were required to maintain MSC survival. Incorporation of these peptides into the hydrogel environment also improved pancreatic islet viability, where combinations of peptides had altered effects on islet survival. GLP-1 alone was the leading stimulator for insulin secretion. Cell adhesion peptides RGDS and IKVAV improved insulin secretion only when they were used in combination, but could not surpass the effect of GLP-1. Further, when pancreatic islets were co-encapsulated with MSCs within synthetic PEG hydrogel, a two-fold increase in the stimulation index was measured. Synergistic effects of MSCs and peptides were observed, with a seven-fold increase in the stimulation index. The results are promising and suggest that simultaneous incorporation of MSCs and ECM-derived peptides and/or GLP-1 can improve pancreatic islet function in response to altered glucose levels in the physiological environment. Copyright © 2014 John Wiley & Sons, Ltd.
Chemical and Biological Engineering, Koc University, Istanbul, Turkey.
Tuğba
T
Bal
Material Sciences and Engineering, Koc University, Istanbul, Turkey.
Caner
C
Nazli
Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.
Alparslan
A
Okcu
Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.
Gökhan
G
Duruksu
Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.|Liv Hospital, Regenerative Medicine, Stem Cell Research and Therapy Center, Istanbul, Turkey.
Erdal
E
Karaöz
Chemical and Biological Engineering, Koc University, Istanbul, Turkey.|Material Sciences and Engineering, Koc University, Istanbul, Turkey.
Seda
S
Kizilel
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D055767:Immobilized Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar
D020100:Hydrogels; D055767:Immobilized Proteins; D007328:Insulin; D008024:Ligands; D010455:Peptides; D011092:Polyethylene Glycols; D020169:Caspases
GLP-1; IKVAV; PEG hydrogel; RGDS; islets; ligand incorporation; mesenchymal stem cells; visible light photopolymerization