Differentiation of human multipotent dermal fibroblasts into islet-like cell clusters

BMC Cell Biol. 2010 Jun 25:11:46. doi: 10.1186/1471-2121-11-46.

Abstract

Background: We have previously obtained a clonal population of cells from human foreskin that is able to differentiate into mesodermal, ectodermal and endodermal progenies. It is of great interest to know whether these cells could be further differentiated into functional insulin-producing cells.

Results: Sixty-one single-cell-derived dermal fibroblast clones were established from human foreskin by limiting dilution culture. Of these, two clones could be differentiated into neuron-, adipocyte- or hepatocyte-like cells under certain culture conditions. In addition, those two clones were able to differentiate into islet-like clusters under pancreatic induction. Insulin, glucagon and somatostatin were detectable at the mRNA and protein levels after induction. Moreover, the islet-like clusters could release insulin in response to glucose in vitro.

Conclusions: This is the first study to demonstrate that dermal fibroblasts can differentiate into insulin-producing cells without genetic manipulation. This may offer a safer cell source for future stem cell-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation
  • Cells, Cultured
  • Clone Cells
  • Dermis / pathology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Foreskin / pathology
  • Glucagon / genetics
  • Glucagon / metabolism
  • Humans
  • Insulin / biosynthesis*
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation
  • Male
  • Pluripotent Stem Cells / metabolism*
  • Pluripotent Stem Cells / pathology
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Transcriptional Activation

Substances

  • Insulin
  • Somatostatin
  • Glucagon