Development of an encapsulated stem cell-based therapy for diabetes

Abstract

Introduction: Islet transplantation can treat the most severe cases of type 1 diabetes but it currently requires deceased donor pancreata as an islet source and chronic immunosuppression to prevent rejection and recurrence of autoimmunity. Stem cell-derived insulin-producing cells may address the shortage of organ donors, whereas cell encapsulation may reduce or eliminate the requirement for immunosuppression, minimizing the risks associated with the islet transplantation procedure, and potentially prolonging graft survival.

Areas covered: This review focuses on the design principles for immunoisolation devices and on stem cell differentiation into insulin-producing cell products. The reader will gain understanding of the different types of immunoisolation devices and the key parameters that affect the outcome of the encapsulated graft. Progresses in stem cell differentiation towards mature endocrine islet cells, including the most recent clinical trials and the challenges associated with the application of immunoisolation devices designed for primary islets to stem-cell products, are also discussed.

Expert opinion: Recent advancements in the field of stem cell-derived islet cell products and immunoisolation strategies hold great promise for type 1 diabetes. However, a combination product including both cells and an immunoisolation strategy still needs to be optimized and tested for safety and efficacy.

Keywords:

• hydrogels
• islet transplantation
• macroencapsulation
• microencapsulation
• scaffold
• vascular supply

Acknowledgments

We apologize to those colleagues whose work we could not cited because of the references limit.

Declaration of interest

AA Tomei and C Ricordi are co-inventors of Intellectual Property discussed in this review and licensed to Converge Biotech. AA Tomei and C Ricordi have a financial interest and stand to gain royalties from the commercialization of the Intellectual Property. C Ricordi is a member of the scientific advisory board and an equity owner in Converge Biotech, licensee of some of the intellectual property used in some of the described studies. Funding was provided by philanthropic funds from the Diabetes Research Institute Foundation, grants from the Juvenile Diabetes Research Foundation (grant # 17-2001-268, 17-2010-5 and 17-2012-361), Converge Biotech, Inc. (Miami, FL, USA), BioRep Technologies, the Fondazione Tronchetti Provera, the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and the National Institute of Health (grant # 5U01DK070460-08 and 5U01DK070431-10). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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