Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Chao-Kai Hsu; Sheng-Pei Wang; Julia Yu-Yun Lee; John A. McGrath

Disclosures

Am J Clin Dermatol. 2014;15(1):1-6. 

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8 Inducible Pluripotent Stem Cells

One of the most significant recent advances in stem cell biology has been the discovery that cells resembling pluripotent embryonic stem cells can be derived from somatic cells such as fibroblasts or keratinocytes by transfection with certain embryonic transcription factors.[34] How best to make use of these cells, known as inducible pluripotent stem cells (iPSCs), for clinical gain is a key question in translational research. Thus far, RDEB cells have been used to make iPSCs[35,36] that can be differentiated into various other cell/tissues, including MSCs containing epithelial progenitors, as originally defined by Tamai et al..[24] iPSCs of RDEB cells can be used for disease modeling or for testing disease-modifying compounds but inherently still possess the same COL7A1 gene defects as the original patient skin. Nevertheless, recent data have shown successful gene editing of these mutant cells which provides encouragement for iPSC gene therapy clinical translation.[12] Aside from gene editing, it may also be plausible to harness the natural gene therapy observed in RDEB keratinocytes: use of such cells in the manufacture and differentiation of iPSCs would avoid the need for additional COL7A1 gene correction and thereby facilitate clinical utility. Use of iPSCs in clinical practice still requires optimization in terms of using non-viral methods of transfection (e.g., using mRNAs or small-molecule manipulation) and other safety data to be established, but the field is changing rapidly and new therapeutic openings are expected shortly. Of note, revertant keratinocytes have been used to produce iPSCs that can be differentiated into an epidermal sheet.[37]

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