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

Mohammadi Ayenehdeh, Jamal; Niknam, Bahare; Hashemi, Seyed Mahmoud; Rahavi, Hossein; Rezaei, Nima; Soleimani, Masoud; Tajik, Nader

doi:10.18869/acadpub.ibj.21.4.218

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

Authors

Jamal Mohammadi Ayenehdeh ¹

Bahare Niknam ²

Seyed Mahmoud Hashemi ³

Hossein Rahavi ²

Nima Rezaei ¹

Masoud Soleimani ⁴

Nader Tajik ²

¹ Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

² Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran

³ Department of Immunology, School of Medicine, Tehran, Shahid Beheshti University of Medical Sciences, Iran

⁴ Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran

10.18869/acadpub.ibj.21.4.218

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. 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