title: Enhanced MIN-6 beta cell survival and function on a nitric oxide-releasing peptide amphiphile nanomatrix.
abstract: Innovative biomaterial strategies are required to improve islet cell retention, viability, and functionality, and thereby obtain clinically successful outcomes from pancreatic islet cell transplantation. To address this need, we have developed a peptide amphiphile-based nanomatrix that incorporates multifunctional bioactive cues and sustained release of nitric oxide. The goal of this study was to evaluate the effect of this peptide amphiphile nanomatrix on the viability and functionality of MIN-6 islet cells. Additionally, this study provides insight into the role of nitric oxide in islet cell biology, given that conventional nitric oxide donors are unable to release nitric oxide in a controlled, sustained manner, leading to ambiguous results. It was hypothesized that controlled nitric oxide release in synergy with multifunctional bioactive cues would promote islet cell viability and functionality. Nitric oxide-releasing peptide amphiphile nanomatrices within the range of 16.25 μmol to 130 μmol were used to analyze MIN-6 cell behavior. Both 32.5 μmol and 65 μmol peptide amphiphiles showed improved MIN-6 functionality in response to glucose over a 7-day time period, and the elevated functionality was correlated with both PDX-1 and insulin gene expression. Our results demonstrate that nitric oxide has a beneficial effect on MIN-6 cells in a concentration-dependent manner.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Lim
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Adinarayana
authors.initials: A
authors.lastname: Andukuri
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA ; Nutech Medical Inc, Division of Endocrinology, Diabetes and Metabolism, Birmingham, AL, USA.
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Vines
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Shibli M
authors.initials: SM
authors.lastname: Rahman
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Patrick Tj
authors.initials: PT
authors.lastname: Hwang
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Birmingham, AL, USA.
authors.forename: Jeonga
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA ; Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Anath
authors.initials: A
authors.lastname: Shalev
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Corbett
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA ; Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Ho-Wook
authors.initials: HW
authors.lastname: Jun
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010455:Peptides; D009569:Nitric Oxide; D005947:Glucose
keywords: beta cells; biomimetic; diabetes; nitric oxide; peptide amphiphile