Transplantation of insulin-secreting cells differentiated from human adipose tissue-derived stem cells into type 2 diabetes mice

Biochem Biophys Res Commun. 2014 Jan 10;443(2):775-81. doi: 10.1016/j.bbrc.2013.10.059. Epub 2013 Oct 19.

Abstract

Currently, there are limited ways to preserve or recover insulin secretory capacity in human pancreas. We evaluated the efficacy of cell therapy using insulin-secreting cells differentiated from human eyelid adipose tissue-derived stem cells (hEAs) into type 2 diabetes mice. After differentiating hEAs into insulin-secreting cells (hEA-ISCs) in vitro, cells were transplanted into a type 2 diabetes mouse model. Serum levels of glucose, insulin and c-peptide were measured, and changes of metabolism and inflammation were assessed in mice that received undifferentiated hEAs (UDC group), differentiated hEA-ISCs (DC group), or sham operation (sham group). Human gene expression and immunohistochemical analysis were done. DC group mice showed improved glucose level, and survival up to 60 days compared to those of UDC and sham group. Significantly increased levels of human insulin and c-peptide were detected in sera of DC mice. RT-PCR and immunohistochemical analysis showed human gene expression and the presence of human cells in kidneys of DC mice. When compared to sham mice, DC mice exhibited lower levels of IL-6, triglyceride and free fatty acids as the control mice. Transplantation of hEA-ISCs lowered blood glucose level in type 2 diabetes mice by increasing circulating insulin level, and ameliorating metabolic parameters including IL-6.

Keywords: Adipose tissue-derived stem cells; DC; Insulin-secreting cells; Interleukin-6; Metabolic parameters; Type 2 diabetes; UDC; differentiated cell; hEA-ISCs; hEAs; human eyelid adipose-derived stem cells; insulin secreting cells differentiated from human eyelid adipose-derived stem cells; undifferentiated cell.

MeSH terms

  • Adipocytes / pathology*
  • Animals
  • Blood Glucose / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / surgery*
  • Female
  • Humans
  • Insulin / blood
  • Insulin-Secreting Cells / pathology*
  • Insulin-Secreting Cells / transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells / pathology*
  • Treatment Outcome

Substances

  • Blood Glucose
  • Insulin