Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

Kruczek, Kamil; Gonzalez‐Cordero, Anai; Goh, Debbie; Naeem, Aabgeena; Jonikas, Mindaugas; Blackford, Samuel J.I.; Kloc, Magdalena; Durán, Yanaí; Georgiadis, Anastasios; Sampson, Robert D.; Maswood, Ryea; Smith, Alexander J.; Decembrini, Sarah; Arsenijévic, Yvan; Sowden, Jane C.; Pearson, R. A.; West, Emma L.; Ali, Robin R.

doi:10.1016/j.stemcr.2017.04.030

Cited by 86 publications

(72 citation statements)

References 46 publications

(113 reference statements)

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“…In another elegant study, improvement of vision impairment was successfully demonstrated following transplantation of functional rod photoreceptors in adult Gnat1 -/mice, which lack rod function as a model of congenital stationary night blindness [78]. Therefore, generation of transplantationcompetent photoreceptor precursors from hPSCs has been investigated to treat blindness [79][80][81][82].…”

Section: (A) Disease Modellingmentioning

confidence: 99%

Three-dimensional cell culture: from evolution to revolution

Alhaque

Themis

Rashidi

2018

Phil. Trans. R. Soc. B

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Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissues Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responses Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids. We also highlight some of the current limitations of these systems and discuss potential avenues to further benefit biological research using three-dimensional modelling technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.

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Section: (A) Disease Modellingmentioning

confidence: 99%

Three-dimensional cell culture: from evolution to revolution

Alhaque

Themis

Rashidi

2018

Phil. Trans. R. Soc. B

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“…Similar findings have been achieved using photoreceptor cells obtained from 3D cultures of pluripotential stem cells (PSCs) from both murine and human sources. [7][8][9] More recently, however, we, and others, [10][11][12] have shown that when transplanted into models of slow or partial degeneration, where significant numbers of recipient photoreceptors still remain, the donor photoreceptors do not integrate within the host retina, but instead undergo an unusual process of material transfer. This involves the robust exchange of material (RNA and/or protein) between donor and host photoreceptors, rendering the host acceptor photoreceptor cells functional.…”

Section: Introductionmentioning

confidence: 98%

Rebuilding the Retina: Prospects for Müller Glial-mediated Self-repair

Langhe

Pearson

2019

Current Eye Research

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Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina. ARTICLE HISTORY Endogenous repair mechanisms CMZ-mediated repairThe CMZ in zebrafish and frogs is well defined and comprised of the ciliary body and the ciliary zone. The ciliary zone consists of

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“…Photoreceptor transplantation is being developed as a therapeutic modality to restore vision in people affected by retinal degenerative diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD) 1–6 . Short term improvements in outer retinal anatomy after photoreceptor cell transplantation have been observed, mainly by histological staining in preclinical models of retinal degeneration 4,7 . However, histology is a relatively inefficient method to track graft and recipient anatomy longitudinally over the long term.…”

Section: Introductionmentioning

confidence: 99%

Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation

Liu

Sodhi

Xue

et al. 2019

Preprint

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32Purpose: Short-term improvements in retinal anatomy are known to occur in preclinical models 33 of photoreceptor transplantation. However, correlative changes over the long term are poorly 34 understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using non-35 invasive multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, to enable serial 36 evaluation of photoreceptor transplantation over the long term. 37Methods: Yellow-green fluorescent microspheres were transplanted into the vitreous cavity 38 and/or subretinal space of C57/BL6J mice. Photoreceptor cell suspensions or sheets from 39 rhodopsin-green fluorescent protein mice were transplanted subretinally, into either NOD.CB17-40 Prkdc scid /J or C3H/HeJ-Pde6b rd1 mice. Multimodal cSLO imaging was performed serially for up 41 to three months after transplantation. Imaging biomarkers were scored, and a grade was defined 42 for each eye by integrating the scores. Image grades were correlated with immunohistochemistry 43 (IHC) data. 44 Results: Multimodal imaging enabled the extraction of quantitative imaging biomarkers 45 including graft size, GFP intensity, graft length, on-target graft placement, intra-graft lamination, 46 hemorrhage, retinal atrophy, and peri-retinal proliferation. Migration of transplanted material 47 increasing the efficiency of preclinical retinal cell transplantation studies in rodents and other 53 animal models. 54 Key words: degenerative retinal diseases, age-related macular degeneration, stem cell therapy, 55 xenotransplantation, photoreceptor cell, retinal organoid, confocal scanning laser 56 ophthalmoscopy 57 Photoreceptor transplantation is being developed as a therapeutic modality to restore vision in 59 people affected by retinal degenerative diseases, including retinitis pigmentosa (RP) and age-60 related macular degeneration (AMD) 1-6 . Short term improvements in outer retinal anatomy after 61 photoreceptor cell transplantation have been observed, mainly by histological staining in 62 preclinical models of retinal degeneration 4,7 . However, histology is a relatively inefficient 63 method to track graft and recipient anatomy longitudinally over the long term. Histological 64 assays are labor-intensive, require large initial cohorts of recipients, and face the challenge of 65 recipient attrition over time. Non-invasive imaging could facilitate the longitudinal evaluation of 66 retinal anatomy in relatively smaller cohorts of recipient animals over time, without the need to 67 sacrifice animals at every assessment time point. 68 Recent advances in imaging techniques have enabled detailed imaging studies in mouse models 69 of retinal disease and regeneration 8-10 . Confocal scanning laser ophthalmoscopy (cSLO) can be 70 used to capture images in multiple imaging modes, including short-wavelength fluorescence 71 (SWF) excitation (488 nm) to detect photoreceptor cells labeled with green fluorescent protein 72 (GFP) in mouse recipients 1 . Multicolor reflectance (MR) imaging combines blue (488 nm)...

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Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

Cited by 86 publications

References 46 publications

Three-dimensional cell culture: from evolution to revolution

Three-dimensional cell culture: from evolution to revolution

Rebuilding the Retina: Prospects for Müller Glial-mediated Self-repair

Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation

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