Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells
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Artur Cieślar-Pobuda1,2, Mehrdad Rafat3, Viktoria Knoflach4, Magdalena Skonieczna2,5, Andrzej Hudecki6, Andrzej Małecki7, Elżbieta Urasińska8, Seaid Ghavami9, Marek J. Łos3,7
1Stem Cell Group, Nordic EMBL Partnership, Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway
2Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland
3LinkoCare Life Sciences AB, Mjärdevi Science Park, Linköping, Sweden
4Unit of Molecular Neurobiology, Department of Medical Biochemistry & Biophysics, Karolinska Institute, Stockholm, Sweden
5Center for Biotechnology, Bioengineering and Bioinformatics, Silesian University of Technology, Gliwice, Poland
6Institute of Non-Ferrous Metals, Gliwice, Poland
7Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland
8Department of Pathology, Pomeranian Medical University, Szczecin, Poland
9Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Marek Łos, email: firstname.lastname@example.org
Keywords: corneal epithelial cells, limbal cells, transdifferentiation, Klf4, Pax6
Received: March 31, 2016 Accepted: May 13, 2016 Published: June 2, 2016
The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches.
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