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bioRxiv · 10.64898/2026.09.12.751148

Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads

Castro Rojas, A.·Brassard, J.·Billaud, M.·Lemaire, F.·Chen, R.·Orimi, H. E.·Tian, J. J.·Paraskevas, S.·Hoesli, C. A.
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Abstract

Pluripotent stem cell-derived pancreatic islet-like cell clusters (SC-islets) have emerged as potential cellular therapy for type 1 diabetes. While SC-islets can theoretically be produced in bioreactors to meet transplantation needs of many recipients per batch, biomanufacturing and translational challenges remain. SC-islet can be cultured in suspension using stirred tank or vertical wheel bioreactors, but these can impart hydrodynamic damage and lead to cellular agglomeration, particularly upon scale-up. We previously described a robust emulsion-based process to encapsulate murine pancreatic beta cells in high-concentration alginate beads which improved graft survival in allogeneic recipients. Here, we present a full pipeline for scalable microencapsulated SC-islet biomanufacturing with extended in vitro bioreactor culture leading into transplantation. We hypothesized that encapsulation would prevent cellular agglomeration, reduce mechanical stress, and preserve differentiation potential during scale-up. Encapsulation of Stage 6 SC-islets prevented cellular agglomeration during extended suspension culture (25 days) and increased cell recovery (91 +/- 3%) compared with non-encapsulated aggregates (60 +/- 10%). No significant differences in glucose-stimulated insulin secretion were observed with vs without microencapsulation. Stage 7 SC-islets matured in the bioreactor were transplanted either as encapsulated islets via the intraperitoneal route or as free SC-islets under the kidney capsule, where they displayed glucose-responsive human C-peptide secretion and remained functional in vivo for up to 98 days. Overall, this work establishes a scalable, robust, transplantation-ready encapsulation platform that supports SC-islet maturation and delivery, providing a generalizable strategy for scaling and transplanting encapsulated organoid systems.

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Castro Rojas, A., Brassard, J., Billaud, M., Lemaire, F., Chen, R., Orimi, H. E., Tian, J. J., Paraskevas, S., Hoesli, C. A.. 2026-09-18. Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads. https://doi.org/10.64898/2026.09.12.751148

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