Mouse and human islets survive and function after coating by biosilicification

Author:

Jaroch David B.12,Lu Jing32,Madangopal Rajtarun12,Stull Natalie D.4567,Stensberg Matthew32,Shi Jin12,Kahn Jennifer L.32,Herrera-Perez Ruth32,Zeitchek Michael32,Sturgis Jennifer8,Robinson J. Paul8,Yoder Mervin C.56,Porterfield D. Marshall1392,Mirmira Raghavendra G.4567,Rickus Jenna L.132

Affiliation:

1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana;

2. Physiological Sensing Facility at the Bindley Bioscience Center and the Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana;

3. Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, Indiana;

4. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana;

5. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana;

6. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana; and

7. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana

8. Purdue University Cytometry Laboratories, Purdue University, West Lafayette, Indiana;

9. Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, Indiana;

Abstract

Inorganic materials have properties that can be advantageous in bioencapsulation for cell transplantation. Our aim was to engineer a hybrid inorganic/soft tissue construct by inducing pancreatic islets to grow an inorganic shell. We created pancreatic islets surrounded by porous silica, which has potential application in the immunoprotection of islets in transplantation therapies for type 1 diabetes. The new method takes advantage of the islet capsule surface as a template for silica formation. Mouse and human islets were exposed to medium containing saturating silicic acid levels for 9–15 min. The resulting tissue constructs were then cultured for up to 4 wk under normal conditions. Scanning electron microscopy and energy dispersive X-ray spectroscopy was used to monitor the morphology and elemental composition of the material at the islet surface. A cytokine assay was used to assess biocompatibility with macrophages. Islet survival and function were assessed by confocal microscopy, glucose-stimulated insulin release assays, oxygen flux at the islet surface, expression of key genes by RT-PCR, and syngeneic transplant into diabetic mice.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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