scholarly journals Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective

2022 ◽  
Vol 23 (2) ◽  
pp. 682
Author(s):  
Raffaele Raimondi ◽  
Piero Zollet ◽  
Francesco Paolo De Rosa ◽  
Panagiotis Tsoutsanis ◽  
Matteo Stravalaci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Replacement Therapy ◽  
Embryonic Stem ◽  
Standard Of Care ◽  
Age Related Macular Degeneration ◽  
Surgical Approaches ◽  
Age Related ◽  
Medical Need ◽  
Pigmented Epithelium ◽  
Induced Pluripotent

The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.

scholarly journals Non-medical treatment for late age-related macular degeneration

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.

scholarly journals Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells

2015 ◽  
Vol 112 (35) ◽  
pp. 10950-10955 ◽  
Author(s):  
Julien Maruotti ◽  
Srinivas R. Sripathi ◽  
Kapil Bharti ◽  
John Fuller ◽  
Karl J. Wahlin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Induced Pluripotent

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.

scholarly journals In vitro differentiation of cGMP-grade retinal pigmented epithelium from human embryonic stem cells

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Fernando H. Lojudice ◽  
Rodrigo A. Brant Fernandes ◽  
Francesco Innocenti ◽  
Carlos E. Franciozi ◽  
Priscila Cristovam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Macular Degeneration ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
World Health ◽  
Retinal Pigmented Epithelium ◽  
Rpe Cells ◽  
Pigmented Epithelium

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.

scholarly journals The Role of E3s in Regulating Pluripotency of Embryonic Stem Cells and Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1168
Author(s):  
Yahong Wu ◽  
Weiwei Zhang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
E3 Ligases ◽  
Somatic Cell Reprogramming ◽  
Age Related ◽  
Induced Pluripotent

Pluripotent embryonic stem cells (ESCs) are derived from early embryos and can differentiate into any type of cells in living organisms. Induced pluripotent stem cells (iPSCs) resemble ESCs, both of which serve as excellent sources to study early embryonic development and realize cell replacement therapies for age-related degenerative diseases and other cell dysfunction-related illnesses. To achieve these valuable applications, comprehensively understanding of the mechanisms underlying pluripotency maintenance and acquisition is critical. Ubiquitination modifies proteins with Ubiquitin (Ub) at the post-translational level to monitor protein stability and activity. It is extensively involved in pluripotency-specific regulatory networks in ESCs and iPSCs. Ubiquitination is achieved by sequential actions of the Ub-activating enzyme E1, Ub-conjugating enzyme E2, and Ub ligase E3. Compared with E1s and E2s, E3s are most abundant, responsible for substrate selectivity and functional diversity. In this review, we focus on E3 ligases to discuss recent progresses in understanding how they regulate pluripotency and somatic cell reprogramming through ubiquitinating core ESC regulators.

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

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.

Sign in / Sign up

Export Citation Format

Share Document