scholarly journals Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration

2018 ◽  
Vol 36 (4) ◽  
pp. 328-337 ◽  
Author(s):  
Lyndon da Cruz ◽  
Kate Fynes ◽  
Odysseas Georgiadis ◽  
Julie Kerby ◽  
Yvonne H Luo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Study ◽  
Retinal Pigment Epithelium ◽  
Embryonic Stem Cell ◽  
Pigment Epithelium ◽  
Phase 1 ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Embryonic stem cell microenvironment enhances proliferation of human retinal pigment epithelium cells by activating the PI3K signaling pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiahui Liu ◽  
Liu Yang ◽  
Xiaoran Wang ◽  
Shoubi Wang ◽  
Zheqian Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Pi3k Signaling ◽  
Age Related ◽  
Pi3k Signaling Pathway

Abstract Background Retinal pigment epithelium (RPE) replacement has been proposed as an efficacious treatment for age-related macular degeneration (AMD), which is the primary cause of vision loss in the elderly worldwide. The embryonic stem cell (ESC) microenvironment has been demonstrated to enable mature cells to gain a powerful proliferative ability and even enhance the stem/progenitor phenotype via activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As the PI3K signaling pathway plays a pivotal role in proliferation and homeostasis of RPE, we hypothesize that the stemness and proliferative capability of RPE can be enhanced by the ESC microenvironment via activation of the PI3K signaling pathway. Methods To investigate whether the ESC microenvironment improves the stem cell phenotype and proliferation properties of human RPE (hRPE) cells by regulating the PI3K signaling pathway, primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 h, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved. Results In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly upregulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells. Conclusions Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.

scholarly journals Ultrathin Polyimide Membrane as Cell Carrier for Subretinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigment Epithelium

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0143669 ◽  
Author(s):  
Tanja Ilmarinen ◽  
Hanna Hiidenmaa ◽  
Peeter Kööbi ◽  
Soile Nymark ◽  
Anni Sorkio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinal Pigment Epithelium ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Polyimide Membrane ◽  
Cell Carrier

scholarly journals Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation

2016 ◽  
Vol 374 (2079) ◽  
pp. 20150376 ◽  
Author(s):  
Junhua Wang ◽  
Peter D. Westenskow ◽  
Mingliang Fang ◽  
Martin Friedlander ◽  
Gary Siuzdak
Keyword(s):  
Stem Cell ◽  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Photoreceptor Degeneration ◽  
Quantitative Metabolomics ◽  
Fatty Acid Amides ◽  
Age Related

Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic ‘fingerprint’ of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all- trans -retinal and its toxic end-product N -retinyl- N -retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation. This article is part of the themed issue ‘Quantitative mass spectrometry’.

scholarly journals Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs

2019 ◽  
Vol 11 (475) ◽  
pp. eaat5580 ◽  
Author(s):  
Ruchi Sharma ◽  
Vladimir Khristov ◽  
Aaron Rising ◽  
Balendu Shekhar Jha ◽  
Roba Dejene ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Clinical Grade ◽  
Functional Validation ◽  
Age Related

Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.

Honeycomb porous films as permeable scaffold materials for human embryonic stem cell-derived retinal pigment epithelium

2016 ◽  
Vol 104 (7) ◽  
pp. 1646-1656 ◽  
Author(s):  
Maria Teresa Calejo ◽  
Tanja Ilmarinen ◽  
Hatai Jongprasitkul ◽  
Heli Skottman ◽  
Minna Kellomäki
Keyword(s):  
Stem Cell ◽  
Retinal Pigment Epithelium ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Porous Films ◽  
Scaffold Materials
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