Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+

Xenotransplantation. Nov-Dec 2012;19(6):355-64. doi: 10.1111/xen.12009.

Abstract

Background: The main hurdles to the widespread use of islet transplantation for the treatment of type 1 diabetes continue to be the insufficient number of appropriate donors and the need for immunosuppression. Microencapsulation has been proposed as a means to protect transplanted islets from the host's immune system.

Methods: This study investigated the function of human pancreatic islets encapsulated in Ca(2+) /Ba(2+) -alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice.

Results: All mice transplanted with encapsulated human islets (n = 29), at a quantity of 3000 islet equivalent (IEQ), achieved normoglycemia 1 day after transplantation and retained normoglycemia for extended periods of time (mean graft survival 134 ± 17 days). In comparison, diabetic Balb/c mice transplanted with an equal amount of non-encapsulated human islets rejected the islets within 2 to 7 days after transplantation (n = 5). Microbeads retrieved after 232 days (n = 3) were found with little to no fibrotic overgrowth and contained viable insulin-positive islets. Immunofluorescent staining on the retrieved microbeads showed F4/80-positive macrophages and alpha smooth muscle actin-positive fibroblasts but no CD3-positive T lymphocytes.

Conclusions: The Ca(2+) /Ba(2+) -alginate microbeads can protect human islets from xenogeneic rejection in immunocompetent mice without immunosuppression. However, grafts ultimately failed likely secondary to a macrophage-mediated foreign body reaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / metabolism
  • Animals
  • Barium / metabolism
  • Calcium / metabolism
  • Diabetes Mellitus, Type 1 / therapy
  • Drug Compounding / methods*
  • Glucuronic Acid / metabolism
  • Graft Survival / immunology
  • Graft Survival / physiology*
  • Hexuronic Acids / metabolism
  • Humans
  • Immunosuppression / methods
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / immunology
  • Islets of Langerhans Transplantation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Microspheres*

Substances

  • Alginates
  • Hexuronic Acids
  • guluronic acid
  • Barium
  • Glucuronic Acid
  • Calcium