Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells

Munenari Itoh, Maija Ht Kiuru, Mitchell S. Cairo, Angela M. Christiano

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Embryonic stem cells (ESCs) have an unlimited proliferative capacity and extensive differentiation capability. They are an alternative source for regenerative therapies with a potential role in the treatment of several human diseases. The clinical use of ESCs, however, has significant ethical and biological obstacles related to their derivation from embryos and potential for immunological rejection, respectively. These disadvantages can be circumvented by the alternative use of induced pluripotent stem cells (iPSCs), which are generated from an individual's (autologous) somatic cells by exogenous expression of defined transcription factors and have biological characteristics similar to ESCs. In recent years, patient-specific iPSCs have been generated to study disease mechanisms and develop iPSC-based therapies. The development of iPSC-based therapies for skin diseases requires successful differentiation of iPSCs into cellular components of the skin, including epidermal keratinocytes. Here, we succeeded in generating iPSCs not only from normal human fibroblasts but also from fibroblasts isolated from the skin of two patients with recessive dystrophic epidermolysis bullosa. Moreover, we differentiated both of these iPSCs into keratinocytes with high efficiency, and generated 3D skin equivalents using iPSC-derived keratinocytes, suggesting that they were fully functional. Our studies indicate that autologous iPSCs have the potential to provide a source of cells for regenerative therapies for specific skin diseases.

Original languageEnglish (US)
Pages (from-to)8797-8802
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number21
DOIs
StatePublished - May 24 2011
Externally publishedYes

Fingerprint

Epidermolysis Bullosa Dystrophica
Induced Pluripotent Stem Cells
Keratinocytes
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Skin Diseases
Skin
Fibroblasts
Transcription Factors
Embryonic Structures

Keywords

  • Bone morphogenetic protein 4
  • Cellular therapy
  • Reprogramming
  • Retinoic acid

ASJC Scopus subject areas

  • General

Cite this

Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells. / Itoh, Munenari; Kiuru, Maija Ht; Cairo, Mitchell S.; Christiano, Angela M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 21, 24.05.2011, p. 8797-8802.

Research output: Contribution to journalArticle

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