Cell Mass Increase Associated with Formation of Glucose-Controlling beta-Cell Mass in Device-Encapsulated Implants of hiPS-Derived Pancreatic Endoderm

Thomas Robert, Ines De Mesmaeker, Freya O Van Hulle, Krista G Suenens, Geert M Stangé, Zhidong Ling, Corinne Haller, Nicolas Bouche, Bart Keymeulen, Marine R C Kraus, Daniel G Pipeleers

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Abstract

Device-encapsulated human stem cell-derived pancreatic endoderm (PE) can generate functional β-cell implants in the subcutis of mice, which has led to the start of clinical studies in type 1 diabetes. Assessment of the formed functional β-cell mass (FBM) and its correlation with in vivo metabolic markers can guide clinical translation. We recently reported ex vivo characteristics of device-encapsulated human embryonic stem cell-derived (hES)-PE implants in mice that had established a metabolically adequate FBM during 50-week follow-up. Cell suspensions from retrieved implants indicated a correlation with the number of formed β cells and their maturation to a functional state comparable to human pancreatic β cells. Variability in metabolic outcome was attributed to differences in number of PE-generated β cells. This variability hinders studies on processes involved in FBM-formation. This study reports modifications that reduce variability. It is undertaken with device-encapsulated human induced pluripotent stem cell-derived-PE subcutaneously implanted in mice. Cell mass of each cell type was determined on intact tissue inside the device to obtain more precise data than following isolation and dispersion. Implants in a preformed pouch generated a glucose-controlling β-cell mass within 20 weeks in over 60% of recipients versus less than 20% in the absence of a pouch, whether the same or threefold higher cell dose had been inserted. In situ analysis of implants indicated a role for pancreatic progenitor cell expansion and endocrine differentiation in achieving the size of β- and α-cell mass that correlated with in vivo markers of metabolic control. Stem Cells Translational Medicine 2019;8:1296&1305.

Original languageEnglish
Pages (from-to)1296-1305
Number of pages10
JournalStem Cells Translational Medicine
Volume8
Issue number12
Early online date4 Aug 2019
DOIs
Publication statusPublished - Dec 2019

Bibliographical note

© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Keywords

  • Cell transplantation
  • Diabetes
  • Induced pluripotent stem cells
  • Pancreatic differentiation
  • Progenitor cells

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