Differentiation of human labia minora dermis-derived fibroblasts into insulin-producing cells

Bona Kim, Byung Sun Yoon, Jai Hee Moon, Jonggun Kim, Eun Kyoung Jun, Jung Han Lee, Jun Sung Kim, Cheong Soon Baik, Aeree Kim, Kwang Youn Whang, Seungkwon You

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Recent evidence has suggested that human skin fibroblasts may represent a novel source of therapeutic stem cells. In this study, we report a 3-stage method to induce the differentiation of skin fibroblasts into insulin- producing cells (IPCs). In stage 1, we establish the isolation, expansion and characterization of mesenchymal stem cells from human labia minora dermis- derived fibroblasts (hLMDFs) (stage 1: MSC expansion). hLMDFs express the typical mesenchymal stem cell marker proteins and can differentiate into adipocytes, osteoblasts, chondrocytes or muscle cells. In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). In stage 3, cells in the mesenchymal- endoderm transition stage are treated with nicotinamide in order to further differentiate into self-assembled, 3-dimensional islet cell-like clusters that express multiple genes related to pancreatic β-cell development and function (stage 3: IPC). We also found that the transplantation of IPCs can normalize blood glucose levels and rescue glucose homeostasis in streptozotocin- induced diabetic mice. These results indicate that hLMDFs have the capacity to differentiate into functionally competent IPCs and represent a potential cell-based treatment for diabetes mellitus.

Original languageEnglish
Pages (from-to)26-35
Number of pages10
JournalExperimental and Molecular Medicine
Volume44
Issue number1
DOIs
Publication statusPublished - 2012 Jan 31

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Keywords

  • Cell differentiation
  • Dermis
  • Endoderm
  • Fibroblasts
  • Humans
  • Insulin
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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