Manufacturing clinical‐grade human induced pluripotent stem cell‐derived beta cells for diabetes treatment

Abstract

The unlimited proliferative capacity of human pluripotent stem cells (hPSCs) fortifies it as one of the most attractive sources for cell therapy application in diabetes. In the past two decades, vast research efforts have been invested in developing strategies to differentiate hPSCs into clinically suitable insulin‐producing endocrine cells or functional beta cells (β cells). With the end goal being clinical translation, it is critical for hPSCs and insulin‐producing β cells to be derived, handled, stored, maintained and expanded with clinical compliance. This review focuses on the key processes and guidelines for clinical translation of human induced pluripotent stem cell (hiPSC)‐derived β cells for diabetes cell therapy. Here, we discuss the (1) key considerations of manufacturing clinical‐grade hiPSCs, (2) scale‐up and differentiation of clinical‐grade hiPSCs into β cells in clinically compliant conditions and (3) mandatory quality control and product release criteria necessitated by various regulatory bodies to approve the use of the cell‐based products.

Innovations in bio-engineering and cell-based approaches to address immunological challenges in islet transplantation

“…This is in contrast with other currently approved autologous therapies such as chimeric antigen receptor (CAR)-T cell immunotherapy which takes 2 to 3 weeks from apheresis to cell infusion. Nonetheless, autologous hiPSC-based cell therapy remains a useful platform for evaluating the safety and efficacy of regenerative medicine treatments for disease without many of the concerns that allogenic transplantations pose ( 164 ).…”

Engineering synthetic poly(ethylene) glycol‐based hydrogels compatible with injection molding biofabrication

“…3 With the advancement and development of manufactured cell products, a means to integrate hydrogel encapsulation into the manufacturing process is desirable to scale combination products, 4 such as in the application of macroencapsulated insulin secreting cell therapies for the treatment of type 1 diabetes. 5 Macroencapsulated cell therapies must balance the delivery of a large number of cells within a single device with oxygen availability to preserve encapsulated cell viability and function, often necessitating complex geometries to achieve this balance. 3,6 We have previously demonstrated the feasibility of hydrogel injection molding complex geometries with natural materials such as alginate and agarose, but synthetic polyethylene glycol (PEG) hydrogels functionalized with the well-characterized and cytocompatible maleimide-thiol Michael-type addition (MTA) chemistry crosslinked too rapidly for successful injection molding.…”

“…Hydrogel injection molding is a promising alternative biofabrication method, useful for rapid and facile generation of complex cell‐laden hydrogel geometries at the patient bedside, and more amenable to high‐throughput manufacturing than existing biofabrication methods 3 . With the advancement and development of manufactured cell products, a means to integrate hydrogel encapsulation into the manufacturing process is desirable to scale combination products, 4 such as in the application of macroencapsulated insulin secreting cell therapies for the treatment of type 1 diabetes 5 . Macroencapsulated cell therapies must balance the delivery of a large number of cells within a single device with oxygen availability to preserve encapsulated cell viability and function, often necessitating complex geometries to achieve this balance 3,6 …”

Complete Suspension Differentiation of Human Pluripotent Stem Cells into Pancreatic Islets Using Vertical Wheel®Bioreactors

“…To date, development of optimized protocols capable of generating sufficient cells for autologous transplantation in patients remains a work in progress. Other protocols have generated high quality-controlled products, however, evidence demonstrating an efficient way to manufacture large batches of SC-islets through these protocols remain a challenge 27 . One potential solution is the adaptation of suspension culture bioreactors (spinner flasks or vertical-wheel ® bioreactors) in SC-islet biomanufacturing.…”