Use of Human Embryonic Stem Cells in the Treatment of Age-Related Macular Degeneration

Abstract Background The World Health Organization (WHO) estimates that the number of individuals who lose their vision due to retinal degeneration is expected to reach 6 million annually in 2020. The retinal degenerative diseases affect the macula, which is responsible for central and detailed vision. Most macular degeneration, i.e., age-related macular degeneration (AMD) develops in the elderly; however, certain hereditary diseases, such as the Stargardt disease, also affect young people. This degeneration begins with loss of retinal pigmented epithelium (RPE) due to formation of drusen (atrophic) or abnormal vessels (exudative). In wet AMD, numerous drugs are available to successful treat the disease; however, no proven therapy currently is available to treat dry AMD or Stargardt. Since its discovery, human embryonic stem cells (hESCs) have been considered a valuable therapeutic tool. Some evidence has shown that transplantation of RPEs differentiated from hESCs cells can result in recovery of both RPE and photoreceptors and prevent visual loss. Methods The human embryonic WA-09 stem cell lineage was cultured under current Good Manufacturing Practices (cGMP) conditions using serum-free media and supplements. The colonies were isolated manually and allowed to spontaneously differentiate into RPE cells. Results This simple and effective protocol required minimal manipulation and yielded more than 10e8 RPE cells by the end of the differentiation and enrichment processes, with cells exhibiting a cobblestone morphology and displaying cellular markers and a gene expression profile typical of mature RPE cells. Moreover, the differentiated cells displayed phagocytic activity and only a small percentage of the total cells remained positive for the Octamer-binding transcriptions factor 4 (OCT-4) pluripotency cell marker. Conclusions These results showed that functional RPE cells can be produced efficiently and suggested the possibility of scaling-up to aim at therapeutic protocols for retinal diseases associated with RPE degeneration.

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Non-medical treatment for late age-related macular degeneration

Clinical ophthalmology ◽

10.32364/2311-7729-2021-21-4-215-219 ◽

2021 ◽

Vol 21 (4) ◽

pp. 215-219

Author(s):

A.K. Drakon ◽

◽

A.G. Kurguzova ◽

V.M. Sheludchenko ◽

N.B. Korchazhkina ◽

...

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Medical Treatment ◽

Macular Degeneration ◽

Retinal Pigment ◽

Embryonic Stem ◽

Age Related Macular Degeneration ◽

Target Cells ◽

Specific Gene ◽

Age Related

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 55 in developed countries. Moreover, the number of these patients will increase growth as life expectancy increases. It is estimated that late AMD accounts for half of blindness and low vision cases in European countries. A myriad of studies is currently underway to discover cutting-edge, effective therapeutic modalities. Gene therapy is a novel alternative to regular intravitreal injections of anti-VEGF agents for late wet AMD. This technique’s heart is a specific gene delivery to target cells to generate natural VEGF inhibitors. Gene therapy affecting the complement system to deactivate its end product, the membrane attack complex, is reasonable in late atrophic AMD. Studies on stem cell therapy for late atrophic AMD undergo as well. It was demonstrated that retinal pigment epithelium (RPE) cells derived from human embryonic stem cells or induced pluripotent stem cells express typical RPE markers that can phagocytize photoreceptor segments. Electrical stimulation and magnet therapy are already introduced into clinical practice to rehabilitate patients with late AMD. Magnetic and electrical fields improve impulse transmitting, activate intracellular and tissue regeneration of the retina. Recent findings are promising but require further in-depth studies. Keywords: age-related macular degeneration, retinal scar, gene therapy, stem cells, physiotherapy, rehabilitative medicine. For citation: Drakon A.K., Kurguzova A.G., Sheludchenko V.M., Korchazhkina N.B. Non-medical treatment for late age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2021;21(4):215–219 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-215-219.

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Investigation of Differentiated Embryonic Stem Cells Growth on Optimized Porous Polymeric Bed with Fuzzy System

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v29i9.7911 ◽

2021 ◽

Author(s):

Saleheh Shahmoradi ◽

Fatemeh Yazdian ◽

Amin Janghorbani ◽

Leila Satarian ◽

Farnaz Behroozi ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Retinal Pigment Epithelium ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Embryonic Stem ◽

Age Related Macular Degeneration ◽

Age Related ◽

Retinal Pigment Epithelium Cells ◽

Epithelium Cells

Introduction: Age-related macular degeneration (AMD) is one of the retina diseases in which retinal pigment epithelium cells are degraded and lead to blindness. Available treatments only slow down the progression of it. In this study, human embryonic stem cells (hESCs) differentiated into retinal pigment epithelium cells were cultured on a polycaprolactone scaffold. Methods: The optimization of the diameter of the produced scaffolds by electrospinning method was done using the fuzzy method for the first time. To improve cell adhesion and proliferation, related parameters to alkaline hydrolysis method were optimized and hydrophobic surface of scaffold was modified. After in vitro analysis, cells were cultured on different groups of scaffolds. In vivo analyses were done and cells culture on scaffolds observed. Results: The optimal parameters for the scaffold based on the fuzzy model were 18.1 kV for voltage, 0.07 g / ml for solution concentration and 115 nm for scaffold diameter, respectively. The immersion time of the scaffold in alkaline solution and concentration of solution were measured 97 min and 3.7 M, respectively. The treated scaffold had a higher degradation rate and water adsorption. MTT-Assay results showed that scaffolds with modified surfaces had a higher amount of cell viability and proliferation after 7 days. SEM image results confirmed this finding after almost two months. Additionally, the results of ICC test showed that after passing this time, cells kept their RPE and epithelium. Conclusion: Based on the results, the hydrolyzed scaffold is a suitable substrate for cell proliferation and can be a good option for AMD treatment.

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Choice of Cell Source in Cell-Based Therapies for Retinal Damage due to Age-Related Macular Degeneration: A Review

Journal of Ophthalmology ◽

10.1155/2013/465169 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Sudhakar John ◽

Sundaram Natarajan ◽

Periyasamy Parikumar ◽

Mahesh Shanmugam P ◽

Rajappa Senthilkumar ◽

...

Keyword(s):

Stem Cells ◽

Macular Degeneration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Embryonic Stem ◽

Age Related Macular Degeneration ◽

Retinal Neurons ◽

Hematopoietic Stem ◽

Age Related ◽

Cell Source

Background. Age-related macular degeneration (AMD) is a complex disorder that affects primarily the macula involving the retinal pigment epithelium (RPE) but also to a certain extent the photoreceptor layer and the retinal neurons. Cell transplantation is a promising option for AMD and clinical trials are underway using different cell types.Methods. We hypothesize that instead of focusing on a particular cell source for concurrent regeneration of all the retinal layers and also to prevent exhaustive research on an array of cell sources for regeneration of each layer, the choice should depend on, precisely, which layer is damaged.Results. Thus, for a damage limited to the retinal pigment epithelial (RPE) layer, the choice we suggest would be RPE cells. When the damage extends to rods and cones, the choice would be bone marrow stem cells and when retinal neurons are involved, relatively immature stem cell populations with an inherent capacity to yield neuronal lineage such as hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells can be tried.Conclusion. This short review will prove to be a valuable guideline for those working on cell therapy for AMD to plan their future directions of research and therapy for this condition.

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