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Islet transplantation and encapsulation: an update on recent developments.

Vijayaganapathy Vaithilingam¹, Bernard E Tuch

¹Diabetes Transplant Unit, Prince of Wales Hospital, University of New South Wales, Sidney NSW 2113, Australia.

The Review of Diabetic Studies : RDS

|July 2, 2011

Summary

Microencapsulating human islets offers a potential alternative to lifelong immunosuppression for type 1 diabetes treatment. However, challenges like biocompatibility and fibrotic overgrowth must be overcome for clinical success.

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Area of Science:

Biotechnology
Immunology
Endocrinology

Background:

Human islet transplantation improves glycemic control in diabetics but requires lifelong immunosuppression with severe side effects.
Microencapsulation aims to shield transplanted islets from immune rejection, eliminating the need for immunosuppressive drugs.
Despite animal model success, encapsulated human islets have not translated to clinical practice.

Purpose of the Study:

To review strategies for overcoming barriers to clinical application of encapsulated human islets.
To enhance the survival and function of encapsulated insulin-producing cells for diabetes therapy.
To address immunological and non-immunological factors hindering microencapsulation success.

Main Methods:

Review of existing literature and research on microencapsulation techniques for islet transplantation.

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Analysis of factors affecting encapsulated islet survival, including biocompatibility, immunoprotection, hypoxia, and fibrotic overgrowth.

Evaluation of the impact of the encapsulation process on human islet transcriptome and function.

Main Results:

Barium alginate microcapsules show biocompatibility in rodents but not in humans, questioning the predictive value of rodent models.
The encapsulation process minimally affected the human islet transcriptome and in vitro/in vivo function.
Significant challenges remain, including biocompatibility and preventing pericapsular fibrotic overgrowth.

Conclusions:

Overcoming non-immunological and immunological barriers is crucial for clinical translation of encapsulated islet technology.
Rodent models may not accurately predict human responses to microencapsulation materials.
Modifications to microcapsule surfaces are needed to prevent fibrotic overgrowth and enable encapsulated islets or surrogates as a viable therapy for type 1 diabetes.