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

ABSTRACT: Device-encapsulated human stem cell-derived pancreatic endoderm (PE) can generate functional ?-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 ?-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 ? cells and their maturation to a functional state comparable to human pancreatic ? cells. Variability in metabolic outcome was attributed to differences in number of PE-generated ? 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 ?-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 ?- and ?-cell mass that correlated with in vivo markers of metabolic control. Stem Cells Translational Medicine 2019;8:1296&1305.

SUBMITTER: Robert T 

PROVIDER: S-EPMC6877770 | biostudies-literature |

REPOSITORIES: biostudies-literature