Human pluripotent stem cells: A toolbox to understand and treat retinal degeneration

Morizur, Lise; Herardot, Elise; Monville, Christelle; M’Barek, Karim Ben

doi:10.1016/j.mcn.2020.103523

Cited by 18 publications

(13 citation statements)

References 178 publications

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“…Finally, the use of stem cell-derived RPE for drug screening constitutes a powerful approach for the development of new agents. Indeed, previous studies have been shown that the safety and efficacy can be enhanced by the use of relevant human cellular models, at the same time that the use of animals for such purpose can be reduced (27,40) CsA, SRL, TAC, and LEF are drugs with known immunosuppressive properties, fully explored as corticosteroid-sparing agents for the treatment of many inflammation processes, including ocular diseases. However, these drugs had their use limited by the poor water solubility and severe side effects.…”

Section: Discussionmentioning

confidence: 99%

Human Stem Cell-Derived Retinal Pigment Epithelial Cells as a Model for Drug Screening and Pre-Clinical Assays Compared to ARPE-19 Cell Line

Oliveira

Paiva

Ribeiro

et al. 2021

IJSC

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Background and Objectives Eye diseases have a high socioeconomic impact on society and may be one of the fields in which most stem cell-related scientific accomplishments have been achieved recently. In this context, human Pluripotent Stem Cell (hPSC) technology arises as an important tool to produce and study human Embryonic Stem cell derived-Retinal Pigmented Epithelial Cells (hES-RPE) for several applications, such as cell therapy, disease modeling, and drug screening. The use of this technology in pre-clinical phases attends to the overall population desire for animal-free product development. Here, we aimed to compare hES-RPE cells with ARPE-19, one of the most commonly used retinal pigmented epithelial immortalized cell lines. Methods and Results Functional, cellular and molecular data obtained suggest that hES-RPE cells more closely resembles native RPEs compared to ARPE-19. Furthermore, hES-RPE revealed an interesting robustness when cultured on human Bruch’s membrane explants and after exposure to Cyclosporine (CSA), Sirolimus (SRL), Tacrolimus (TAC), Leflunomide (LEF) and Teriflunomide (TER). On these conditions, hES-RPE cells were able to survive at higher drug concentrations, while ARPE-19 cell line was more susceptible to cell death. Conclusions Therefore, hES-RPEs seem to have the ability to incur a broader range of RPE functions than ARPE-19 and should be more thoroughly explored for drug screening.

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Section: Discussionmentioning

confidence: 99%

Human Stem Cell-Derived Retinal Pigment Epithelial Cells as a Model for Drug Screening and Pre-Clinical Assays Compared to ARPE-19 Cell Line

Oliveira

Paiva

Ribeiro

et al. 2021

IJSC

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“…In the last decade, several protocols based on spontaneous differentiation have been developed to convert hPSCs into RPE cells [7,[18][19][20]. The differentiation is initiated by FGF2 withdrawal (used to maintain the pluripotency state of hPSCs).…”

Section: Hpsc-based Cell Therapy: Selected Examples 231 Retinal Degenerationmentioning

confidence: 99%

“…In some instances, multiple cell types may be combined to improve cell integration and functionality. This is the case when multiple cell types degenerate or when a microenvironment should be recreated [7,61,63,64,96,97,110]. Stimulation of the vascularization of the grafted hPSC-derived tissue (i.e., muscle, heart, skin) is also required for its long-term survival and integration [61,63,64,98,110,114].…”

Section: Limitations/challengesmentioning

confidence: 99%

“…The vast majority of transplanted PR precursors were later found to remain in the subretinal space where they engaged in a process of material transfer of functional proteins with host PRs [43][44][45]160,161]. The precise mechanism of this material exchange between PRs remains elusive but preclinical studies clearly demonstrated that this exchange occurs only with donor PR precursors and not with other cell types [7,160]. It could involve direct donor/host plasma membrane fusion or other methods of intercellular trafficking including EVs [162].…”

Section: Tissue Restoration In the Eyementioning

confidence: 99%

“…Besides the therapeutic effects of cells elicited by their direct presence, some of the observed benefits are mediated by their indirect actions and, as such, may not require Cells 2021, 10, 240 2 of 29 them [6,7]. Extracellular vesicles (EVs) have emerged as important mediators of paracrine signaling and could exert such functions [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Future of Regenerative Medicine: Cell Therapy Using Pluripotent Stem Cells and Acellular Therapies Based on Extracellular Vesicles

Jarrige

Frank

Herardot

et al. 2021

Cells

Self Cite

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The rapid progress in the field of stem cell research has laid strong foundations for their use in regenerative medicine applications of injured or diseased tissues. Growing evidences indicate that some observed therapeutic outcomes of stem cell-based therapy are due to paracrine effects rather than long-term engraftment and survival of transplanted cells. Given their ability to cross biological barriers and mediate intercellular information transfer of bioactive molecules, extracellular vesicles are being explored as potential cell-free therapeutic agents. In this review, we first discuss the state of the art of regenerative medicine and its current limitations and challenges, with particular attention on pluripotent stem cell-derived products to repair organs like the eye, heart, skeletal muscle and skin. We then focus on emerging beneficial roles of extracellular vesicles to alleviate these pathological conditions and address hurdles and operational issues of this acellular strategy. Finally, we discuss future directions and examine how careful integration of different approaches presented in this review could help to potentiate therapeutic results in preclinical models and their good manufacturing practice (GMP) implementation for future clinical trials.

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Biomechanical Characterization of Retinal Pigment Epitheliums Derived from hPSCs Using Atomic Force Microscopy

Herardot,

Liboz,

Lamour

et al. 2024

Stem Cell Rev and Rep

Self Cite

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The retinal pigment epithelium (RPE), a multifunctional cell monolayer located at the back of the eye, plays a crucial role in the survival and homeostasis of photoreceptors. Dysfunction or death of RPE cells leads to retinal degeneration and subsequent vision loss, such as in Age-related macular degeneration and some forms of Retinitis Pigmentosa. Therefore, regenerative medicine that aims to replace RPE cells by new cells obtained from the differentiation of human pluripotent stem cells, is the focus of intensive research. However, despite their critical interest in therapy, there is a lack of biomechanical RPE surface description. Such biomechanical properties are tightly related to their functions. Herein, we used atomic force microscopy (AFM) to analyze both the structural and mechanical properties of RPEs obtained from four cell lines and at different stages of epithelial formation. To characterize epitheliums, we used apical markers in immunofluorescence and showed the increase of transepithelial resistance, as well as the ability to secrete cytokines with an apico-basal polarity. Then, we used AFM to scan the apical surface of living or fixed RPE cells. We show that RPE monolayers underwent softening of apical cell center as well as stiffening of cell borders over epithelial formation. We also observed apical protrusions that depend on actin network, suggesting the formation of microvilli at the surface of RPE epitheliums. These RPE cell characteristics are essential for their functions into the retina and AFM studies may improve the characterization of the RPE epithelium suitable for cell therapy. Graphical Abstract

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Human pluripotent stem cells: A toolbox to understand and treat retinal degeneration

Cited by 18 publications

References 178 publications

Human Stem Cell-Derived Retinal Pigment Epithelial Cells as a Model for Drug Screening and Pre-Clinical Assays Compared to ARPE-19 Cell Line

Human Stem Cell-Derived Retinal Pigment Epithelial Cells as a Model for Drug Screening and Pre-Clinical Assays Compared to ARPE-19 Cell Line

The Future of Regenerative Medicine: Cell Therapy Using Pluripotent Stem Cells and Acellular Therapies Based on Extracellular Vesicles

Biomechanical Characterization of Retinal Pigment Epitheliums Derived from hPSCs Using Atomic Force Microscopy

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