Advancing islet transplantation: From engraftment to the immune response

R. F. Gibly, J. G. Graham, X. Luo, W. L. Lowe, B. J. Hering, L. D. Shea*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations

Abstract

The promise and progress of islet transplantation for treating type 1 diabetes has been challenged by obstacles to patient accessibility and long-term graft function that may be overcome by integrating emerging technologies in biomaterials, drug delivery and immunomodulation. The hepatic microenvironment and traditional systemic immunosuppression stress the vulnerable islets and contribute to the limited success of transplantation. Locally delivering extracellular matrix proteins and trophic factors can enhance transplantation at extrahepatic sites by promoting islet engraftment, revascularisation and long-term function while avoiding unintended systemic effects. Cell- and cytokine-based therapies for immune cell recruitment and reprogramming can inhibit local and systemic immune system activation that normally attacks transplanted islets. Combined with antigen-specific immunotherapies, states of operational tolerance may be achievable, reducing or eliminating the long-term pharmaceutical burden. Integration of these technologies to enhance engraftment and combat rejection may help to advance the therapeutic efficacy and availability of islet transplantation.

Original languageEnglish (US)
Pages (from-to)2494-2505
Number of pages12
JournalDiabetologia
Volume54
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Biomaterial
  • Biotechnology
  • Diabetes
  • Extrahepatic
  • Immunomodulation
  • Islet transplantation
  • Review
  • Scaffold
  • Tissue engineering
  • Tolerance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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