gms | German Medical Science

23rd Annual Meeting of the German Retina Society

German Retina Society

24.09. - 25.09.2010, Freiburg

Generation of retinal pigment epithelial cells from human iPS cells reprogrammed using two exogenous transcription factors and small molecules

Meeting Abstract

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  • Tim U. Krohne - University Eye Clinic Bonn

German Retina Society. 23rd Annual Conference of the German Retina Society. Freiburg i. Br., 24.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10rg53

doi: 10.3205/10rg53, urn:nbn:de:0183-10rg531

This is the translated version of the article.
The original version can be found at: http://www.egms.de/de/meetings/rg2010/10rg53.shtml

Published: September 21, 2010

© 2010 Krohne.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

The recent development of technologies capable of producing induced pluripotent stem (iPS) cells from adult somatic tissues may permit their use to generate autologous retinal pigment epithelium (RPE) grafts for the treatment of diseases like age-related macular degeneration (AMD). Current reprogramming techniques require retroviral transduction of four transcription factors which in part possess oncogenic potential. Given the associated risk of tumor formation, the use of iPS cells reprogrammed with a reduced number of these factors would be advantageous. We therefore evaluated human iPS cells that were generated using only two exogenous transcription factors for their capacity to differentiate into RPE cells. iPS cells were generated from primary human epidermal keratinocytes by lentiviral two factors transduction (Oct4, Klf4) and additional treatment with small molecules or, alternatively, from human fibroblasts using standard four factor transduction (Oct4, Sox2, Nanog, Lin28). RPE cells could be differentiated from both two factor- and four factor-derived iPS cells. These cells exhibited homogenous polygonal morphology and pronounced pigmentation, formed epithelial monolayers with intracellular tight junctions, and expressed RPE-specific markers (bestrophin, CRALBP, RPE65). Moreover, the cells phagocytosed photoreceptor outer segments and exhibited barrier function with apical-to-basolateral fluid transport. Thus, we demonstrate the capability of two factor-derived human iPS cells to differentiate into cells with RPE-specific morphology and function. Further optimization of reprogramming and differentiation efficiency is crucial for future therapeutic application of iPS cell-derived RPE cells as autologous grafts in diseases like AMD.