Millimeter-thick xenoislet-laden fibers as retrievable transplants mitigate foreign body reactions for long-term glycemic control in diabetic mice

Takaichi Watanabe, Teru Okitsu, Fumisato Ozawa, Shogo Nagata, Hitomi Matsunari, Hiroshi Nagashima, Masaki Nagaya, Hiroki Teramae, Shoji Takeuchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Transplantation technologies of pancreatic islets as well as stem cell-derived pancreatic beta cells encapsulated in hydrogel for the induction of immunoprotection could advance to treat type 1 diabetes mellitus, if the hydrogel transplants acquire retrievability through mitigating foreign body reactions after transplantation. Here, we demonstrate that the diameter of the fiber-shaped hydrogel transplants determines both in vivo cellular deposition onto themselves and their retrievability. Specifically, we found that the in vivo cellular deposition is significantly mitigated when the diameter is 1.0 mm and larger, and that 1.0 mm-thick xenoislet-laden fiber-shaped hydrogel transplants can be retrieved after being placed in the intraperitoneal cavities of immunocompetent diabetic mice for more than 100 days, during which period the hydrogel transplants can normalize the blood glucose concentrations of the mice. These findings could provide an innovative concept of a transplant that would promote the clinical application of stem cell-derived functional cells through improving their in vivo efficacy and safety.

Original languageEnglish
Article number120162
JournalBiomaterials
Volume255
DOIs
Publication statusPublished - Oct 2020
Externally publishedYes

Keywords

  • Alginate
  • Immunoprotection
  • Islet encapsulation
  • Regenerative medicine
  • Retrievable graft
  • Xenotransplantation

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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