Reduction of Activin A gives rise to comparable expression of key definitive endoderm and mature beta cell markers

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Regen Med. 2024 Jan;19(1):47-63. 

Aldyn Wildey 1Stephen Harrington 1Lisa Stehno-Bittel 1 2Francis Karanu 1

Affiliations expand

Abstract

Aim: Cell therapies for diabetes rely on differentiation of stem cells into insulin-producing cells, which is complex and expensive. Our goal was to evaluate production costs and test ways to reduce it. Methods: Cost of Goods (COGs) analysis for differentiation was completed and the effects of replacement or reduction of the most expensive item was tested using qRT-PCR, immunohistochemistry, flow cytometry along with glucose-stimulated insulin release. Results: Activin A (AA) was responsible for significant cost. Replacement with small molecules failed to form definitive endoderm (DE). Reducing AA by 50% did not negatively affect expression of beta cell markers. Conclusion: Reduction of AA concentration is feasible without adversely affecting DE and islet-like cell differentiation, leading to significant cost savings in manufacturing.

Keywords: Activin A; cost of goods analysis; differentiation; human induced pluripotent stem cells; islet-like cells.

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