Stem Cell Derived Retinal Pigment Epithelium

Autor: Arthur A.B. Bergen, L. A. E. Catsburg, Vivi M. Heine, Reinier O. Schlingemann, J. van Meurs, Perry D. Moerland, Céline Koster, J.B. ten Brink, Theo G. M. F. Gorgels, Anna Bennis, J. G. Jacobs
Přispěvatelé: ANS - Complex Trait Genetics, AR&D - Amsterdam Reproduction & Development, Graduate School, ACS - Amsterdam Cardiovascular Sciences, ANS - Amsterdam Neuroscience, Ophthalmology, Other departments, APH - Personalized Medicine, APH - Methodology, Epidemiology and Data Science, Human Genetics, ACS - Atherosclerosis & ischemic syndromes, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Netherlands Institute for Neuroscience (NIN), Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pediatric surgery, Human genetics, Amsterdam Reproduction & Development (AR&D), MUMC+: *AB Onderzoekers (9), Oogheelkunde, RS: FHML non-thematic output
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Cellular differentiation
Gene Expression
0302 clinical medicine
OXIDATIVE STRESS
Induced pluripotent stem cell
Age related macular degeneration
Genetics
Pigmentation
Cell Polarity
Cell Differentiation
Cell biology
medicine.anatomical_structure
VISUAL FUNCTION
DIFFERENTIATION
Human embryonic stem cells
Stem cell
Visual phototransduction
Signal Transduction
Pluripotent Stem Cells
MELATONIN
Biology
Article
Cell Line
PHAGOCYTOSIS
03 medical and health sciences
AGE
medicine
Cell Adhesion
Journal Article
Humans
RPE CELLS
Transcriptomics
Retinal pigment epithelium
TRANSPLANTATION
Gene Expression Profiling
Cell Biology
MACULAR DEGENERATION
Embryonic stem cell
eye diseases
Gene expression profiling
Transplantation
030104 developmental biology
Tissue Array Analysis
030221 ophthalmology & optometry
Cell replacement therapy
sense organs
INTEGRIN-LINKED KINASE
Biomarkers
Transcription Factors
Zdroj: STEM CELL REVIEWS AND REPORTS, 13(5), 659-669. Humana Press
Bennis, A, Jacobs, J G, Catsburg, L A E, ten Brink, J B, Koster, C, Schlingemann, R O, van Meurs, J, Gorgels, T G M F, Moerland, P D, Heine, V M & Bergen, A A 2017, ' Stem Cell Derived Retinal Pigment Epithelium : The Role of Pigmentation as Maturation Marker and Gene Expression Profile Comparison with Human Endogenous Retinal Pigment Epithelium ', Stem Cell Reviews and Reports, vol. 13, no. 5, pp. 659-669 . https://doi.org/10.1007/s12015-017-9754-0
Stem cell reviews and reports, 13(5), 659-669. Humana Press
Stem Cell Reviews and Reports, 13, 659-669. Humana Press
Stem Cell Reviews
Bennis, A, Jacobs, J G, Catsburg, L A E, Ten Brink, J B, Koster, C, Schlingemann, R O, van Meurs, J, Gorgels, T G M F, Moerland, P D, Heine, V M & Bergen, A A 2017, ' Stem Cell Derived Retinal Pigment Epithelium : The Role of Pigmentation as Maturation Marker and Gene Expression Profile Comparison with Human Endogenous Retinal Pigment Epithelium ', Stem cell reviews and reports, vol. 13, no. 5, pp. 659-669 . https://doi.org/10.1007/s12015-017-9754-0
Stem Cell Reviews and Reports, 13(5), 659-669. Humana Press
Stem Cell Reviews and Reports, 13(5), 659-669. Springer
ISSN: 1558-6804
2629-3269
2629-3277
1550-8943
DOI: 10.1007/s12015-017-9754-0
Popis: In age-related macular degeneration (AMD) the retinal pigment epithelium (RPE) deteriorates, leading to photoreceptor decay and severe vision loss. New therapeutic strategies aim at RPE replacement by transplantation of pluripotent stem cell (PSC)-derived RPE. Several protocols to generate RPE have been developed where appearance of pigmentation is commonly used as indicator of RPE differentiation and maturation. It is, however, unclear how different pigmentation stages reflect developmental stages and functionality of PSC-derived RPE cells. We generated human embryonic stem cell-derived RPE (hESC-RPE) cells and investigated their gene expression profiles at early pigmentation (EP) and late pigmentation (LP) stages. In addition, we compared the hESC-RPE samples with human endogenous RPE. We used a common reference design microarray (44 K). Our analysis showed that maturing hESC-RPE, upon acquiring pigmentation, expresses markers specific for human RPE. Interestingly, our analysis revealed that EP and LP hESC-RPE do not differ much in gene expression. Our data further showed that pigmented hESC-RPE has a significant lower expression than human endogenous RPE in the visual cycle and oxidative stress pathways. In contrast, we observed a significantly higher expression of pathways related to the process adhesion-to-polarity model that is typical of developing epithelial cells. We conclude that, in vitro, the first appearance of pigmentation hallmarks differentiated RPE. However, further increase in pigmentation does not result in much significant gene expression changes and does not add important RPE functionalities. Consequently, our results suggest that the time span for obtaining differentiated hESC-RPE cells, that are suitable for transplantation, may be greatly reduced. Electronic supplementary material The online version of this article (doi:10.1007/s12015-017-9754-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE