Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes

Abstract

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long‐term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. In this progress report, the design considerations and functional requirements of macroencapsulation systems are reviewed, specifically for stem‐cell derived islets (SC‐islets), highlighting distinct design parameters. Additionally, a perspective on the future for macroencapsulation systems is given, and how incorporating continuous sensing and closed‐loop feedback can be transformative in advancing toward an autonomous biohybrid artificial pancreas.

Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform

“…Looking towards the future, living implants containing stem cell-derived pancreatic β-cells represent a potential cure for diabetes. However, the attenuation of oxygen and molecular transport due to the FC barrier still constitutes a major hurdle to successful clinical translation of these implants 9,10,18,19 . It is evident that a method to (i) mitigate the FBR or (ii) improve transport across the FC could transform the management of this pervasive disease.…”

Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

“…The ideal islet encapsulation device needs to keep sufficient grafts functional to regulate blood glucose, be biocompatible, insulate grafts from the immune system, and make nutrition and oxygen available for maintaining cell viability (Korsgren, 2017 ; Jiang et al, 2022 ). Optimization of cell encapsulation strategy shows promise for circumventing immunosuppressive therapy (Desai and Shea, 2017 ; Goswami et al, 2021 ). For example, the human PSC-derived β cells encapsulated with triazole-thiomorpholine dioxide alginate showed long-term glycemic control and mitigated immune response after transplantation into immunocompetent mice (Vegas et al, 2016 ).…”

Engineering the next generation of cell-based therapeutics

“…Larger-sized cell encapsulation systems (that is, macrodevices) offer potential safety benefits because they can be designed to be retrievable after implantation 203 . This benefit has been leveraged to advance cell sources with higher safety risk assessments (that is, stem cell-derived or transformed cells) that have potential for tumorigenesis or teratoma formation into human clinical testing (NCT02239354).…”