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Microporous Scaffolds Drive Assembly and Maturation of Progenitors into β-Cell Clusters

27 Pages Posted: 26 Feb 2019 First Look: Accepted

See all articles by Richard L. Youngblood

Richard L. Youngblood

University of Michigan at Ann Arbor - Department of Biomedical Engineering

Joshua P. Sampson

University of Michigan at Ann Arbor - Department of Biomedical Engineering

Kimberly R. Lebioda

University of Michigan at Ann Arbor - Department of Biomedical Engineering

Graham Spicer

University of Michigan at Ann Arbor - Department of Biomedical Engineering

Lonnie D. Shea

University of Michigan at Ann Arbor - Department of Biomedical Engineering

Abstract

Human pluripotent stem cells (hPSCs) represent a promising cell source for the development of β-cells for use in therapies for type 1 diabetes. Current culture approaches provide the signals to drive differentiation towards β-cells, with the cells spontaneously assembling into clusters. Herein, we adapted the current culture systems to cells seeded on microporous biomaterials, with the hypothesis that the pores can guide the assembly into β-cell clusters of defined size that can enhance maturation. The microporous scaffold culture allows hPSC-derived pancreatic progenitors to form clusters at a consistent size as cells undergo differentiation to immature β-cells. By modulating the scaffold pore sizes, we observed 250-425 µm pore size scaffolds significantly enhance insulin expression and key β-cell maturation markers compared to suspension cultures. Furthermore, when compared to suspension cultures, the scaffold culture showed increased insulin secretion in response to glucose stimulus indicating the development of functional β-cells. In addition, scaffolds facilitated cell-cell interactions enabled by the scaffold design and cell-mediated matrix deposition of extracellular matrix (ECM) proteins associated with the basement membrane of islet cells. We further investigated the influence of ECM on cell development by incorporating an ECM matrix on the scaffold prior to cell seeding; however, their presence did not further enhance maturation. These results suggest the microporous scaffold culture facilitates 3D cluster formation, supports cell-cell interactions, and provides a matrix similar to a basement membrane to drive in vitro hPSC-derived β-cell maturation and demonstrates the feasibility of these scaffolds as a biomanufacturing platform.

Keywords: biomaterials, stem cell culture, diabetes, regenerative medicine

Suggested Citation

Youngblood, Richard L. and Sampson, Joshua P. and Lebioda, Kimberly R. and Spicer, Graham and Shea, Lonnie D., Microporous Scaffolds Drive Assembly and Maturation of Progenitors into β-Cell Clusters (February 26, 2019). Available at SSRN: https://ssrn.com/abstract=3339836

Richard L. Youngblood (Contact Author)

University of Michigan at Ann Arbor - Department of Biomedical Engineering

500 S. State Street
Ann Arbor, MI 48109
United States

Joshua P. Sampson

University of Michigan at Ann Arbor - Department of Biomedical Engineering

500 S. State Street
Ann Arbor, MI 48109
United States

Kimberly R. Lebioda

University of Michigan at Ann Arbor - Department of Biomedical Engineering

500 S. State Street
Ann Arbor, MI 48109
United States

Graham Spicer

University of Michigan at Ann Arbor - Department of Biomedical Engineering

500 S. State Street
Ann Arbor, MI 48109
United States

Lonnie D. Shea

University of Michigan at Ann Arbor - Department of Biomedical Engineering ( email )

500 S. State Street
Ann Arbor, MI 48109
United States

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