Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival

Shuxian Hu*, Rei Kuwabara, Carlos E Navarro Chica, Alexandra M Smink, Taco Koster, Juan D Medina, Bart J de Haan, Martin Beukema, Jonathan R T Lakey, Andrés J García, Paul de Vos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
40 Downloads (Pure)

Abstract

Encapsulation of pancreatic islets in alginate-microcapsules is used to reduce or avoid the application of life-long immunosuppression in preventing rejection. Long-term graft function, however, is limited due to varying degrees of host tissue responses against the capsules. Major graft-longevity limiting responses include inflammatory responses provoked by biomaterials and islet-derived danger-associated molecular patterns (DAMPs). This paper reports on a novel strategy for engineering alginate microcapsules presenting immunomodulatory polymer pectin with varying degrees of methyl-esterification (DM) to reduce these host tissue responses. DM18-pectin/alginate microcapsules show a significant decrease of DAMP-induced Toll-Like Receptor-2 mediated immune activation in vitro, and reduce peri-capsular fibrosis in vivo in mice compared to higher DM-pectin/alginate microcapsules and conventional alginate microcapsules. By testing efficacy of DM18-pectin/alginate microcapsules in vivo, we demonstrate that low-DM pectin support long-term survival of xenotransplanted rat islets in diabetic mice. This study provides a novel strategy to attenuate host responses by creating immunomodulatory capsule surfaces that attenuate activation of specific pro-inflammatory immune receptors locally at the transplantation site.

Original languageEnglish
Article number120460
Pages (from-to)1-13
Number of pages13
JournalBiomaterials
Volume266
Early online date2020
DOIs
Publication statusPublished - Jan-2021

Keywords

  • Pectin
  • Microcapsule
  • Tissue response
  • Toll-Like Receptor
  • Danger-associated molecular pattern
  • Type 1 diabetes
  • MOLECULAR-PATTERNS
  • CELL-ENCAPSULATION
  • PANCREATIC-ISLETS
  • XENOTRANSPLANTATION
  • BIOCOMPATIBILITY
  • IMMUNOISOLATION
  • ACTIVATION
  • CHALLENGES
  • TOLERANCE
  • CHEMISTRY

Cite this