Cell-matrix Interactions Improve Beta-cell Survival and Insulin Secretion in Three-dimensional Culture
Overview
Biomedical Engineering
Biotechnology
Affiliations
Controlled matrix interactions were presented to pancreatic beta-cells in three-dimensional culture within poly(ethylene glycol) hydrogels. Dispersed MIN6 beta-cells were encapsulated in gel environments containing the following entrapped extracellular matrix (ECM) proteins: collagen type I, collagen type IV, fibrinogen, fibronectin, laminin, and vitronectin. In ECM-containing gels, beta-cell survival was significantly better than in gels without ECM over 10 days. Correspondingly, apoptosis in encapsulated beta-cells was less in the presence of each matrix protein, suggesting the ability of individual matrix interactions to prevent matrix signaling-related apoptosis (anoikis). MIN6 beta-cells cultured in gels containing collagen type IV or laminin secreted more insulin in response to glucose stimulation than beta-cells in all other experimental conditions. Variations in collagen type IV or laminin concentration between 10 microg/mL and 250 microg/mL did not affect insulin secretion. Finally, beta-cell function in hydrogels presenting both collagen type IV and laminin revealed synergistic interactions. With a total protein concentration of 100 microg/mL, three gel compositions of varying ratios of collagen type IV to laminin (25:75, 50:50, and 75:25) were tested. In the presence of 25 microg/mL of collagen type IV and 75 microg/mL of laminin, beta-cell insulin secretion was greater than with laminin or collagen type IV individually. These results demonstrate that specific, rationally designed extracellular environments promote isolated beta-cell survival and function.
The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner.
Okuyama T, Tsuno T, Inoue R, Fukushima S, Kyohara M, Matsumura A iScience. 2025; 28(2):111856.
PMID: 39995864 PMC: 11848788. DOI: 10.1016/j.isci.2025.111856.
Jeyagaran A, Urbanczyk M, Carvajal-Berrio D, Baldissera T, Kaiser P, Kuhlburger L Adv Healthc Mater. 2024; 14(2):e2403017.
PMID: 39511898 PMC: 11730087. DOI: 10.1002/adhm.202403017.
Perlecan: An Islet Basement Membrane Protein with Protective Anti-Inflammatory Characteristics.
Brandhorst D, Brandhorst H, Acreman S, Johnson P Bioengineering (Basel). 2024; 11(8).
PMID: 39199786 PMC: 11351669. DOI: 10.3390/bioengineering11080828.
Karakaya E, Gleichauf L, Schobel L, Hassan A, Soufivand A, Tessmar J RSC Adv. 2024; 14(20):13769-13786.
PMID: 38681843 PMC: 11046382. DOI: 10.1039/d3ra08394b.
A vascularized 3D model of the human pancreatic islet forstudy of immune cell-islet interaction.
Bender R, ODonnell B, Shergill B, Pham B, Tahmouresie S, Sanchez C Biofabrication. 2023; 16(2).
PMID: 38128127 PMC: 10782895. DOI: 10.1088/1758-5090/ad17d0.