Enhancing the Functionality of Immunoisolated Human SC-βeta Cell Clusters through Prior Resizing

Matthew A Bochenek; Ben Walters; Jingping Zhang; Owen S Fenton; Amanda Facklam; Zuzana Kroneková; Michal Pelach; Elise N Engquist; Nayara C Leite; Alex Morgart; Igor Lacík; Robert Langer; Daniel G Anderson

doi:10.1002/smll.202307464

Enhancing the Functionality of Immunoisolated Human SC-βeta Cell Clusters through Prior Resizing

Small. 2024 Jan 11:e2307464. doi: 10.1002/smll.202307464. Online ahead of print.

Authors

Matthew A Bochenek^{1

2

3}, Ben Walters^{1

2

3}, Jingping Zhang⁴, Owen S Fenton^{1

2}, Amanda Facklam^{1

5}, Zuzana Kroneková⁶, Michal Pelach⁶, Elise N Engquist⁴, Nayara C Leite⁴, Alex Morgart^{1

2

3}, Igor Lacík⁶, Robert Langer^{1

2

3

7

8}, Daniel G Anderson^{1

2

3

7

8}

Affiliations

¹ David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA.
² Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
³ Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA.
⁴ Harvard University, 7 Divinity Avenue, Cambridge, MA, 02138, USA.
⁵ Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
⁶ Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, 845 41, Slovakia.
⁷ Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
⁸ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.

PMID: 38212275
DOI: 10.1002/smll.202307464

Abstract

The transplantation of immunoisolated stem cell derived beta cell clusters (SC-β) has the potential to restore physiological glycemic control in patients with type I diabetes. This strategy is attractive as it uses a renewable β-cell source without the need for systemic immune suppression. SC-β cells have been shown to reverse diabetes in immune compromised mice when transplanted as ≈300 µm diameter clusters into sites where they can become revascularized. However, immunoisolated SC-β clusters are not directly revascularized and rely on slower diffusion of nutrients through a membrane. It is hypothesized that smaller SC-β cell clusters (≈150 µm diameter), more similar to islets, will perform better within immunoisolation devices due to enhanced mass transport. To test this, SC-β cells are resized into small clusters, encapsulated in alginate spheres, and coated with a biocompatible A10 polycation coating that resists fibrosis. After transplantation into diabetic immune competent C57BL/6 mice, the "resized" SC-β cells plus the A10 biocompatible polycation coating induced long-term euglycemia in the mice (6 months). After retrieval, the resized A10 SC-β cells exhibited the least amount of fibrosis and enhanced markers of β-cell maturation. The utilization of small SC-β cell clusters within immunoprotection devices may improve clinical translation in the future.

Keywords: cell encapsulation; diabetes; immune isolation devices; stem cell beta cells; transplantation.

Abstract

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