Introducing a New Experimental Islet Transplantation Model using Biomimetic Hydrogel and a Simple High Yield Islet Isolation Technique

Iran Biomed J. 2017 Jul;21(4):218-27. doi: 10.18869/acadpub.ibj.21.4.218. Epub 2017 Jun 6.

Abstract

Background: Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus (T1DM). This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial.

Methods: The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct. In comparison with conventional methods, we inflated the pancreas in Petri dishes with only 1 ml collagenase type XI solution, which was followed by hand-picking isolation or Ficoll gradient separation to purify the islets. Then we used a hydrogel composite in which the islets were embedded and transplanted into the peritoneal cavity of the streptozotocin-induced diabetic C57BL/6 mice.

Results: As compared to the yield of the classical methods, in our modified technique, the mean yield of isolation was about 130-200 viable islets/mouse pancreas. In vitro glucose-mediated insulin secretion assay indicated an appropriate response in isolated islets. In addition, data from in vivo experiments revealed that the allograft remarkably maintained blood glucose levels under 400 mg/dl and hydrogel composite prevents the passage of immune cells.

Conclusion: In the model presented here, the rapid islet isolation technique and the application of biomimetic hydrogel wrapping of islets could facilitate islet transplantation procedures.

Keywords: Islet pancreas; Isolation; Transplantation; Type 1 diabetes mellitus.

MeSH terms

  • Animals
  • Biomimetic Materials / pharmacology*
  • Blood Glucose
  • Ficoll
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation / methods*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL

Substances

  • Blood Glucose
  • Insulin
  • Ficoll
  • Hydrogel, Polyethylene Glycol Dimethacrylate