Differentiation of human labia minora dermis-derived fibroblasts into insulin-producing cells
Experimental & Molecular Medicine
;
: 26-35, 2012.
Article
in English
| WPRIM
| ID: wpr-211721
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transferrin
/
Biomarkers
/
Cell Differentiation
/
Trans-Activators
/
Cell Separation
/
Cells, Cultured
/
Islets of Langerhans Transplantation
/
Niacinamide
/
Sodium Selenite
/
Homeodomain Proteins
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2012
Type:
Article
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