Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads
- 1McGill University
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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BibTeX
@misc{rojas2026bridging,
title = {{Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads}},
author = {A. Castro Rojas and J. Brassard and M. Billaud and F. Lemaire and R. Chen and H. E. Orimi and J. J. Tian and S. Paraskevas and C. A. Hoesli},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.12.751148},
url = {https://www.biorxiv.org/content/10.64898/2026.09.12.751148v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads
AU - A. Castro Rojas
AU - J. Brassard
AU - M. Billaud
AU - F. Lemaire
AU - R. Chen
AU - H. E. Orimi
AU - J. J. Tian
AU - S. Paraskevas
AU - C. A. Hoesli
PY - 2026
DA - 2026/09/12
PB - bioRxiv
DO - 10.64898/2026.09.12.751148
UR - https://www.biorxiv.org/content/10.64898/2026.09.12.751148v1
AB - 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.
ER -