Journal article
Induction of trabecular meshwork cells from induced pluripotent stem cells
Investigative ophthalmology & visual science, Vol.55(11), pp.7065-7072
10/08/2014
DOI: 10.1167/iovs.14-14800
PMCID: PMC4224582
PMID: 25298418
Abstract
Loss or dysfunction of trabecular meshwork (TM) cells has been associated with the development of pathologically elevated IOP, and it is conceivable that replacement of damaged TM cells could restore function to the TM. We propose that the use of TM-like cells derived from induced pluripotent stem cells (iPSCs) created from a patient's own dermal fibroblasts offers the best solution to this challenge. Here we demonstrate that mouse iPSCs can be induced to differentiate into TM-like cells suitable for autologous transplantation. Directed induction of stem cell differentiation was achieved through coculture of mouse iPSCs with human TM cells for up to 21 days. The resultant TM-like cells (iPSC-TM) were characterized morphologically, immunohistochemically, and functionally. The iPSC-TM cells closely resembled cultured human TM cells morphologically and began to express many markers of TM cells while ceasing to express pluripotency markers such as Nanog, Oct4, and Sox2. Functionally, these cells developed the ability to phagocytose particles. Finally, exposure to dexamethasone or phorbol 12-myristate acetate caused a distinct increase in the production and secretion of myocilin and matrix metalloproteinase-3, respectively, behavior characteristic of TM cells. Our data demonstrate that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. Not only do these cells represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM, resulting in re-establishment of IOP.
Details
- Title: Subtitle
- Induction of trabecular meshwork cells from induced pluripotent stem cells
- Creators
- Qiong J Ding - University of IowaWei Zhu - University of IowaAmy C Cook - University of IowaKristin R Anfinson - University of IowaBudd A Tucker - University of IowaMarkus H Kuehn - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.55(11), pp.7065-7072
- Publisher
- United States
- DOI
- 10.1167/iovs.14-14800
- PMID
- 25298418
- PMCID
- PMC4224582
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Grant note
- R01EY022044 / NEI NIH HHS I01 RX001163 / RRD VA R01 EY022044 / NEI NIH HHS
- Language
- English
- Date published
- 10/08/2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980072802771
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