GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation

Stem Cell Reports. 2022 Apr 12;17(4):964-978. doi: 10.1016/j.stemcr.2022.03.004. Epub 2022 Mar 31.

Abstract

Human pluripotent stem cell (hPSC)-derived pancreatic progenitors (PPs) can be differentiated into beta-like cells in vitro and in vivo and therefore have therapeutic potential for type 1 diabetes (T1D) treatment. However, the purity of PPs varies across different hPSC lines, differentiation protocols, and laboratories. The uncommitted cells may give rise to non-pancreatic endodermal, mesodermal, or ectodermal derivatives in vivo, hampering the safety of hPSC-derived PPs for clinical applications and their differentiation efficiency in research settings. Recently, proteomics and transcriptomics analyses identified glycoprotein 2 (GP2) as a PP-specific cell surface marker. The GP2-enriched PPs generate higher percentages of beta-like cells in vitro, but their potential in vivo remains to be elucidated. Here, we demonstrate that the GP2-enriched-PPs give rise to all pancreatic cells in vivo, including functional beta-like cells. Remarkably, GP2 enrichment eliminates the risk of teratomas, which establishes GP2 sorting as an effective method for PP purification and safe pancreatic differentiation.

Keywords: beta cells; cell replacement therapy; cell surface marker; ectoderm; endoderm; human embryonic stem cells; mesoderm; pancreatic progenitors; teratoma; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology
  • Endoderm
  • Humans
  • Insulin-Secreting Cells* / metabolism
  • Pancreas
  • Pluripotent Stem Cells* / metabolism
  • Teratoma* / etiology
  • Teratoma* / metabolism

Grant support