Modeling spatial distribution of oxygen in 3d culture of islet beta-cells.
Three-dimensional (3D) scaffold culture of pancreatic β-cell has been proven to be able to better mimic physiological conditions in the body. However, one critical issue with culturing pancreatic β-cells is that β-cells consume large amounts of oxygen, and hence insufficient oxygen supply in the culture leads to loss of β-cell mass and functions. This becomes more significant when cells are cultured in a 3D scaffold. In this study, in order to understand the effect of oxygen tension inside a cell-laden collagen culture on β-cell proliferation, a culture model with encapsulation of an oxygen-generator was established. The oxygen-generator was made by embedding hydrogen peroxide into nontoxic polydimethylsiloxane to avoid the toxicity of a chemical reaction in the β-cell culture. To examine the effectiveness of the oxygenation enabled 3D culture, the spatial-temporal distribution of oxygen tension inside a scaffold was evaluated by a mathematical modeling approach. Our simulation results indicated that an oxygenation-aided 3D culture would augment the oxygen supply required for the β-cells. Furthermore, we identified that cell seeding density and the capacity of the oxygenator are two critical parameters in the optimization of the culture. Notably, cell-laden scaffold cultures with an in situ oxygen supply significantly improved the β-cells' biological function. These β-cells possess high insulin secretion capacity. The results obtained in this work would provide valuable information for optimizing and encouraging functional β-cell cultures. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:221-228, 2017.
Dept. of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701.
John
J
McReynolds
Dept. of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701.
Yu
Y
Wen
Dept. of Materials Science & Engineering, The Ohio State University, Columbus, OH.
Xiaofei
X
Li
Dept. of Materials Science & Engineering, The Ohio State University, Columbus, OH.
Jianjun
J
Guan
Dept. of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR, 72701.|Dept. of Biomedical engineering, Thomas J. Watson School of Engineering and Applied Sciences, State University of New York in Binghamton, Binghamton, NY, 13902.
Sha
0000-0002-8033-8110
S
Jin
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation / Q000235:genetics; D003094:Collagen / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D010100:Oxygen / Q000378:metabolism*
D007328:Insulin; D003094:Collagen; D006861:Hydrogen Peroxide; D010100:Oxygen
insulin; oxygen; pancreatic β-cells; simulation; three dimensional culture