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

Tijdschriftbijdrage - Tijdschriftartikel

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.

Tijdschrift: Stem Cells Translational Medicine
ISSN: 2157-6564
Issue: 12
Volume: 8
Pagina's: 1296-1305
Aantal pagina's: 10
Jaar van publicatie:2019
Trefwoorden:Cell transplantation, Diabetes, Induced pluripotent stem cells, Pancreatic differentiation, Progenitor cells, Celbiologie
  • Scopus Id: 85070772847
  • DOI: https://doi.org/10.1002/sctm.19-0043
  • ORCID: /0000-0002-6440-2485/work/65269983
  • ORCID: /0000-0003-3148-1372/work/65269991
  • ORCID: /0000-0002-8671-4527/work/65270998