Differentiation of human labia minora dermis-derived fibroblasts into insulin-producing cells.
10.3858/emm.2012.44.1.002
- Author:
Bona KIM
1
;
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
Author Information
1. Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Korea. bioseung@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell differentiation;
dermis;
endoderm;
fibroblasts;
humans;
insulin;
mesenchymal stem cells
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(1):26-35
- CountryRepublic of Korea
- Language:English
-
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.
