Background

Human pluripotent stem cell (hPSC)-derived pancreatic islets show significant promise for cell replacement therapies in type 1 diabetes, but the current differentiation protocols often produce heterogeneous cultures containing immature endocrine cells and unwanted non-endocrine populations. Achieving reproducible differentiation across multiple stem cell lines while maintaining endocrine purity remains a key challenge in the development of clinically relevant stem cell therapies.  

Biolaminin® contribution

In this study, Wu et al. developed an optimized differentiation protocol that consistently generated functional stem cell-derived pancreatic islets (SC-islets) from eight different human pluripotent stem cell lines. Biolaminin 521 (LN-521) was utilized during two-dimensional endocrine progenitor differentiation as part of the optimized differentiation workflow. The researchers found that combining Biolaminin 521 with a shortened pancreatic progenitor stage significantly improved the generation of NKX6.1+/NEURO1+ endocrine progenitor cells, an important intermediate cell population in pancreatic endocrine development. When compared with longer differentiation conditions, the optimized LN-521 workflow increased SC-islet formation and produced a higher proportion of insulin-producing β cells.

Transitioning endocrine progenitor cells into three-dimensional aggregates further enriched endocrine populations while selectively removing proliferative and non-endocrine cells. The resulting SC-islets displayed high endocrine purity and robust glucose-responsive insulin and C-peptide secretion, demonstrating the ability of the cells to sense changes in glucose concentration and respond through regulated insulin secretion, a defining characteristic of functional pancreatic β cells. Single-cell transcriptomic analysis further confirmed the absence of detectable non-endocrine populations and revealed endocrine cell compositions consistent with mature pancreatic islets.

Clinical translation and future applications

Following intraocular transplantation into diabetic mice, the SC-islets restored glycemic control, produced human C-peptide, and continued to mature in vivo.  Collectively, these findings demonstrate that Biolaminin 521 supports a robust and reproducible pancreatic differentiation workflow capable of generating highly functional SC-islets with improved endocrine purity across multiple pluripotent stem cell lines. The resulting SC-islets exhibited functional characteristics in vitro and continued to mature following transplantation, highlighting their potential of this optimized differentiation strategy for future cell therapy applications.

Cited study: Wu S et al. An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines. Stem Cell Reports (2026). https://doi.org/10.1016/j.stemcr.2026.102892

Product used in this study:

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  Biolaminin 521 LN (LN521)

  Full-length human recombinant laminin-521

  Biolaminin 521 LN is a full-length laminin-521 substrate—the natural laminin for pluripotent stem cells, reliably facilitating ESC and iPSC self-r […]
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