Compositions and methods for stem cell growth

The use of TGF-β and Hippo pathway inhibitors in dissociated stem cell cultures enhances cell cluster formation and pluripotency, addressing limitations in three-dimensional cell culture expansion for pancreatic islet therapy.

WO2026136809A1PCT designated stage Publication Date: 2026-06-25VERTEX PHARMACEUTICALS INC
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Patent Information

Application Number
PCT/US2025/060542
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-08-29
Filing Date
2025-12-19
Publication Date
2026-06-25

AI Technical Summary

Technical Problem

Limited stem cell expansion in three-dimensional cell culture prevents effective implementation of artificial pancreatic islets therapy for diabetes, necessitating improved methods for in vitro stem cell expansion that mimic endogenous pancreatic islet function and characteristics.

Method used

Compositions and methods involving TGF-β pathway inhibitors and/or Hippo pathway inhibitors, without a gel matrix, are used to enhance stem cell expansion, with at least 25% of cells dissociated, and optionally agitated in a bioreactor, using specific inhibitors like Alk5 inhibitor II, A 83-01, and GA-017, and media such as StemScale and DMEM/F12, to increase cell cluster formation and pluripotency.

Benefits of technology

The methods result in significant increases in cell clusters and pluripotency, with up to 1000% increase in cell clusters and high expression of OCT4 and SOX2, facilitating effective stem cell expansion for pancreatic islet therapy.

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Abstract

Disclosed herein are compositions and methods related to a plurality of stem cells administered a TGF-beta pathway inhibitor and / or a Hippo pathway inhibitor. In some embodiments, the composition does not comprise a gel matrix and / or either mesenchymal stem cells or cancer stem cells. In some embodiments, at least 25% of the cells in the composition are dissociated. In some embodiments, the stem cells are agitated in the composition.
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