Differentiation of human labia minora dermis-derived fibroblasts into insulin-producing cells.
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.
Laboratory of Cell Function Regulation College of Life Sciences and Biotechnology Korea University Seoul, Korea.
Bona
B
Kim
Byung Sun
BS
Yoon
Jai Hee
JH
Moon
Jonggun
J
Kim
Eun Kyoung
EK
Jun
Jung Han
JH
Lee
Jun Sung
JS
Kim
Cheong Soon
CS
Baik
Aeree
A
Kim
Kwang Youn
KY
Whang
Seungkwon
S
You
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology* / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005836:Genitalia, Female / Q000166:cytology*; D005947:Glucose / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009536:Niacinamide / Q000494:pharmacology; D020127:Recovery of Function; D055760:SOXF Transcription Factors / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology
D015415:Biomarkers; C496502:FOXA2 protein, human; D018398:Homeodomain Proteins; D007328:Insulin; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; D015534:Trans-Activators; D014168:Transferrin; C084010:pancreatic and duodenal homeobox 1 protein; D051542:Hepatocyte Nuclear Factor 3-beta; D009536:Niacinamide; D018038:Sodium Selenite; D005947:Glucose