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Stem Cells Transl Med. 2019 Aug 4. doi: 10.1002/sctm.19-0043. [Epub ahead of print]

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

Author information

1
Diabetes Research Center, Brussels Free University-VUB, Brussels, Belgium.
2
Beta Cell Therapy Consortium, Brussels, Belgium.
3
University Hospital Brussels-UZB, Brussels, Belgium.
4
Nestlé Research, Lausanne, Switzerland.

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.

KEYWORDS:

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

PMID:
31379140
DOI:
10.1002/sctm.19-0043
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