Cell Mass Increase Associated with Formation of Glucose-Controlling β-Cell Mass in Device-Encapsulated Implants of hiPS-Derived Pancreatic Endoderm. (4th August 2019)

• Record Type: Journal Article
• Authors: Robert, Thomas; De Mesmaeker, Ines; Van Hulle, Freya O.; Suenens, Krista G.; Stangé, Geert M.; Ling, Zhidong; Haller, Corinne; Bouche, Nicolas; Keymeulen, Bart; Kraus, Marine R.C.; Pipeleers, Daniel G.
• Is Part Of: Stem cells translational medicine. Volume 8:Number 12(2019)
• Page Start: 1296
• Page End: 1305
• Publication Date: 2019-08-04
• Subjects: Diabetes -- Induced pluripotent stem cells -- Pancreatic differentiation -- Cell transplantation -- Progenitor cells; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.19-0043
• Languages: English
• ISSNs: 2157-6564

Abstract

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 : Abstract : Device-encapsulated human induced pluripotent stem cell-derived pancreatic endoderm can generate a glucose-controlling β-cell mass in immune-compromised mice. For a dose of 5 × 10 6 cells, this involves pancreatic progenitor cell differentiation as well as a cell mass increase following an initial cell loss. Measurement of these processes inside the device allows selection of conditions that help achieve metabolic control.