Collagen IV-modified scaffolds improve islet survival and function and reduce time to euglycemia

Woon Teck Yap, David M. Salvay, Michael A. Silliman, Xiaomin Zhang, Zachary G. Bannon, Dixon B. Kaufman, William L. Lowe, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Islet transplantation on extracellular matrix (ECM) protein-modified biodegradable microporous poly(lactide-co-glycolide) scaffolds is a potential curative treatment for type 1 diabetes mellitus (T1DM). Collagen IV-modified scaffolds, relative to control scaffolds, significantly decreased the time required to restore euglycemia from 17 to 3 days. We investigated the processes by which collagen IV-modified scaffolds enhanced islet function and mediated early restoration of euglycemia post-transplantation. We characterized the effect of collagen IV-modified scaffolds on islet survival, metabolism, and insulin secretion in vitro and early- and intermediate-term islet mass and vascular density post-transplantation and correlated these with early restoration of euglycemia in a syngeneic mouse model. Control scaffolds maintained native islet morphologies and architectures as well as collagen IV-modified scaffolds in vivo. The islet size and vascular density increased, while β-cell proliferation decreased from day 16 to 113 post-transplantation. Collagen IV-modified scaffolds promoted islet cell viability and decreased early-stage apoptosis in islet cells in vitro - phenomena that coincided with enhanced islet metabolic function and glucose-stimulated insulin secretion. These findings suggest that collagen IV-modified scaffolds promote the early restoration of euglycemia post-transplantation by enhancing islet metabolism and glucose-stimulated insulin secretion. These studies of ECM proteins, in particular collagen IV, and islet function provide key insights for the engineering of a microenvironment that would serve as a platform for enhancing islet transplantation as a viable clinical therapy for T1DM.

Original languageEnglish (US)
Pages (from-to)2361-2372
Number of pages12
JournalTissue Engineering - Part A
Volume19
Issue number21-22
DOIs
StatePublished - Jan 1 2013

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ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Yap, W. T., Salvay, D. M., Silliman, M. A., Zhang, X., Bannon, Z. G., Kaufman, D. B., Lowe, W. L., & Shea, L. D. (2013). Collagen IV-modified scaffolds improve islet survival and function and reduce time to euglycemia. Tissue Engineering - Part A, 19(21-22), 2361-2372. https://doi.org/10.1089/ten.tea.2013.0033