Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice

Nutr Res. 2015 Jul;35(7):603-9. doi: 10.1016/j.nutres.2015.05.009. Epub 2015 May 22.

Abstract

Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients.

Keywords: C57BL/KsJ-Lep(db/+) mouse model; Gestational diabetes mellitus; Human embryonic stem cell–derived pancreatic endoderm; Hyperglycemia; Hyperinsulinemia; Stem cell therapy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Cell Differentiation
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / therapy*
  • Endoderm*
  • Female
  • Fetal Development
  • Human Embryonic Stem Cells / physiology*
  • Humans
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Pancreas*
  • Pregnancy
  • Pregnancy Outcome*
  • Tissue Transplantation

Substances

  • Blood Glucose