Exp Mol Med.  2012 Jan;44(1):26-35. 10.3858/emm.2012.44.1.002.

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

• Kim B
• Yoon BS
• Moon JH
• Kim J
• Jun EK
• Lee JH
• Kim JS
• Baik CS
• Kim A
• Whang KY
• You S

• KMID: 1120139
• DOI: http://doi.org/10.3858/emm.2012.44.1.002

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 beta-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.

Keyword

cell differentiation; dermis; endoderm; fibroblasts; humans; insulin; mesenchymal stem cells

MeSH Terms

Animals
Biological Markers/metabolism
*Cell Culture Techniques
*Cell Differentiation
Cell Proliferation/drug effects
Cell Separation
Cells, Cultured
Dermis/*cytology/drug effects
Diabetes Mellitus, Experimental/*surgery
Female
Fibroblasts/*cytology/drug effects
Genitalia, Female/*cytology
Glucose/metabolism
Hepatocyte Nuclear Factor 3-beta/metabolism
Homeodomain Proteins/metabolism
Humans
Insulin/pharmacology/secretion
Insulin-Secreting Cells/*cytology/metabolism
*Islets of Langerhans Transplantation
Mesenchymal Stem Cells/*cytology/drug effects/metabolism
Mice
Mice, Nude
Niacinamide/pharmacology
Recovery of Function
SOXF Transcription Factors/metabolism
Sodium Selenite/pharmacology
Trans-Activators/metabolism
Transferrin/pharmacology