Journal article
Connective Tissue Growth Factor Promotes Efficient Generation of Human Induced Pluripotent Stem Cell‐Derived Choroidal Endothelium
Stem Cells Translational Medicine, Vol.6(6), pp.1533-1546
2017
DOI: 10.1002/sctm.16-0399
PMCID: PMC5689757
PMID: 28474838
Abstract
Age‐related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, the majority of stem cell research to date has focused on production of retinal pigment epithelial (RPE) and photoreceptor cells for the purpose of evaluating disease pathophysiology and cell replacement, there is strong evidence that the choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first to be lost in this disease. As such, to accurately evaluate disease pathophysiology and develop an effective treatment, production of patient‐specific, stem cell‐derived CECs will be required. In this study, we report for the first time a stepwise differentiation protocol suitable for generating human iPSC‐derived CEC‐like cells. RNA‐seq analysis of the monkey CEC line, RF/6A, combined with two statistical screens allowed us to develop media comprised of various protein combinations. In both screens, connective tissue growth factor (CTGF) was identified as the key component required for driving CEC development. A second factor tumor necrosis factor (TNF)‐related weak inducer of apoptosis receptor was also found to promote iPSC to CEC differentiation by inducing endogenous CTGF secretion. CTGF‐driven iPSC‐derived CEC‐like cells formed capillary tube‐like vascular networks, and expressed the EC‐specific markers CD31, ICAM1, PLVAP, vWF, and the CEC‐restricted marker CA4. In combination with RPE and photoreceptor cells, patient‐specific iPSC derived CEC‐like cells will enable scientists to accurately evaluate AMD pathophysiology and develop effective cell replacement therapies. S tem C ells T ranslational M edicine 2017;6:1533–1546
Details
- Title: Subtitle
- Connective Tissue Growth Factor Promotes Efficient Generation of Human Induced Pluripotent Stem Cell‐Derived Choroidal Endothelium
- Creators
- Allison E Songstad - Wynn Institute for vision researchKristan S Worthington - Wynn Institute for vision researchKathleen R Chirco - Wynn Institute for vision researchJoseph C Giacalone - Wynn Institute for vision researchS. Scott Whitmore - Wynn Institute for vision researchKristin R Anfinson - Wynn Institute for vision researchDalyz Ochoa - Wynn Institute for vision researchCathryn M Cranston - Wynn Institute for vision researchMegan J Riker - Wynn Institute for vision researchMaurine Neiman - University of IowaEdwin M Stone - Wynn Institute for vision researchRobert F Mullins - Wynn Institute for vision researchBudd A Tucker - Wynn Institute for vision research
- Resource Type
- Journal article
- Publication Details
- Stem Cells Translational Medicine, Vol.6(6), pp.1533-1546
- DOI
- 10.1002/sctm.16-0399
- PMID
- 28474838
- PMCID
- PMC5689757
- NLM abbreviation
- Stem Cells Transl Med
- ISSN
- 2157-6564
- eISSN
- 2157-6580
- Publisher
- John Wiley and Sons Inc; Hoboken
- Alternative title
- CTGF Drives Choroidal Endothelium Development
- Language
- English
- Date published
- 2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Gender, Women's and Sexuality Studies; Biology; Chemical and Biochemical Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980087102771
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