Experimental stem cell replacement transplantation in retinal pigment epithelium atrophy

Нероева, Н. В.; Нероев, В. В.; Катаргина, Л. А.; Ryabina, M. V.; Ilyukhin, P. A.; Karmokova, A. G.; Лосанова, О. А.; Maybogin, A. M.; Kharitonov, A E; Eremeev, A V; Lagarkova, Maria A.

doi:10.17116/oftalma20221380317

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…Помимо развития и оптимизации методологии получения клеток для целей регенеративной медицины необходимо также учитывать особенности самой процедуры трансплантации и важность снижения рисков послеоперационных осложнений. Ряд исследований направлен на повышение безопасности манипуляций с сетчаткой, например смещение инъекционного пузыря в сторону от места укола [49] или герметизацию места введения с помощью аутологичной плазмы, обогащённой тромбоцитами [50]. В то же время совершенствование хирургических методов позволяет варьировать степень повреждения сетчатки и таким образом моделировать проявления наследственных заболеваний in vivo [51].…”

Section: дифференцировка индуцированных плюрипотентных стволовых клет...unclassified

Features of generation and differentiation of induced pluripotent stem cells into retinal cells for modeling human hereditary diseases

Lapshin,

Gershovich,

Minskaya

et al. 2024

Genes & Cells

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Currently, numerous studies demonstrate the possibility of generating human iPSCs from somatic cells, which ensures the rapid progress of research in human diseases for which there are no relevant animal models or limited access to primary human tissues and cells. The utilization of technology for generation of iPSCs with their subsequent differentiation is, among other things, a promising approach for studying the disease pathogenesis and developing methods for treating optical neuropathies and retinopathy - the most common types of pathologies of the visual system, in which degeneration of retinal ganglion cells occurs (and, as a consequence, optic nerve atrophy) or pigment epithelial cells and photoreceptors are affected, respectively. This review presents a variety of protocols for generating iPSCs from somatic cells and their subsequent differentiation, with an emphasis on the observed biological effects of the resulting cell cultures, including organoids, and also discusses the prospects of using such models. The article may be useful to researchers studying the pathogenesis of various hereditary forms of blindness and developers of approaches for the treatment of these diseases who need to obtain a relevant cellular model.

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Section: дифференцировка индуцированных плюрипотентных стволовых клет...unclassified

Features of generation and differentiation of induced pluripotent stem cells into retinal cells for modeling human hereditary diseases

Lapshin,

Gershovich,

Minskaya

et al. 2024

Genes & Cells

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Surgical methods of retinal pigment epithelium transplantation in rabbits in experiment

Нероева

Lagarkova

Ilyukhin

et al. 2023

Ophthalmology Reports

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The article is devoted to the study of surgical methods of retinal pigment epithelium transplantation in experiment on rabbits. The history of retinal pigment epithelium transplantation is briefly characterized in the study. Characteristics of the methods used are presented, their limitations, possibilities, and requirements for implementation in practice are highlighted. The results of transplantation of suspension of retinal pigment epithelium cells differentiated from human induced pluripotent stem cells (IPSC-RPE) without and with the use of platelet-rich blood plasma (PRP) are also considered. According to the results of the analysis we have developed modified methods of IPSC-RPE cells transplantation in the experiment on rabbits, which allow to reduce the number of postoperative complications, which provides the best therapeutic effect. Prospects for further studies are associated with a comparative analysis of the proposed techniques in terms of cell survival at different terms, anatomical integration and functional efficiency in the dynamics.

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Clinical and Immunological Analysis of Retinal Pigment Epithelium Transplantation Derived from Induced Pluripotent Stem Cells under Pharmacological Immunosuppression in Rabbits

Neroeva,

Balatskaya,

Brilliantova

et al. 2024

Oftalʹmologiâ

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justification. Degenerative retinal diseases associated with retinal pigment epithelium damage are untreated and lead to irreversible vision loss. The most promising approach nowadays is considered to be the transplantation of retinal pigment epithelium differentiated from pluripotent stem cells (PSC-RPE). When testing biomedical cellular products, special requirements are placed on the animal model, which should simulate pathological changes, such as in humans, and have sufficient immunological tolerance to xenogenic human cells, enabling them to function fully. For this purpose, lines of immuno-modified or immunodeficiency animals are used, usually small rodents (rats and mice), but the small size and structure of their eyes do not allow manipulation in vitreoretinal interventions in humans. An alternative method of preventing xenotransplantation rejection in large models is pharmacological immunosuppression, under which transplanted PSC-RPE may have biological effects. However, targeted studies of the effectiveness of PSC-RPE transplantation with use of immunosuppressive therapy have not been conducted in our country, and the data of a few foreign works devoted to this problem are contraversial.Purpose. Study of immunological reactivity in transplantation of IPSC-RPE under combined immunosuppressive therapy in rabbit experiment.Materials and methods. The study was performed on 27 male rabbits of New Zealand albino breed, of which 24 animals underwent subretinal transplantation of induced pluripotent stem cells of retinal pigment epithelium: in the I group (12 eyes) intervention was performed in the healthy eye; in group II (12 eyes) — in the area of pre-modeled atrophy of retinal pigment epithelium. Recipients were given combined immunosuppressive therapy. Control Group — 3 intact rabbits (6 eyes). The observation period was 14, 28 and 60 days. Post-transplant evaluation was carried out using standard and specialized ophthalmological examination methods. The determination of cytokines of the immune response IL-2, IL-6, immunosuppressive factors TGF-β1, TGF-β2, TSP-1 in the serum of the blood and the vitreous body was performed by solid-phase immunosurgical enzyme analysis.Results. Comprehensive analysis of biomicroscopy, ophthalmoscopy, optical coherent tomography, immunological studies revealed no signs of active inflammation; no local and systemic increase in the concentration of acute phase IL-6, a drop in serum IL-2 levels indicated direct effects of immunosuppressive drug combinations used in this study.Conclusion. The use of combined immunosuppressive therapy prevented rejection of xenogenic material in rabbits and obtained evidence of safety of subretinal transplantation of IPSC-RPE suspension both in the healthy eye, and pre-induced atrophy of pigmentary epithelium.

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Experimental stem cell replacement transplantation in retinal pigment epithelium atrophy

Cited by 4 publications

References 17 publications

Features of generation and differentiation of induced pluripotent stem cells into retinal cells for modeling human hereditary diseases

Features of generation and differentiation of induced pluripotent stem cells into retinal cells for modeling human hereditary diseases

Surgical methods of retinal pigment epithelium transplantation in rabbits in experiment

Clinical and Immunological Analysis of Retinal Pigment Epithelium Transplantation Derived from Induced Pluripotent Stem Cells under Pharmacological Immunosuppression in Rabbits

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