Differentiation of Retinal Organoids from Human Pluripotent Stem Cells

Chichagova, Valeria; Dorgau, Birthe; Felemban, Majed; Γεωργίου, Μαρία; Armstrong, Lyle; Lako, Majlinda

doi:10.1002/cpsc.95

Cited by 30 publications

(25 citation statements)

References 23 publications

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“…For optogenetic strategies, retinal organoids also provide an interesting model for pre-clinical testing. Whilst they do not perfectly replicate the neural retina, distinctive layers of different cell types have been shown across different research groups using similar protocols (Zhong et al, 2014;Reichman et al, 2017;Quinn et al, 2018;Chichagova et al, 2019). A consistent feature across all protocols appears to be a lack of photoreceptor outer segment structures, but this does not pose a problem for testing of optogenetic vectors as indeed it mimics the absence of such structures in retinitis pigmentosa.…”

Section: Human-derived Retinal Organoidsmentioning

confidence: 99%

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

et al. 2020

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The degeneration of light-detecting rod and cone photoreceptors in the human retina leads to severe visual impairment and ultimately legal blindness in millions of people worldwide. Multiple therapeutic options at different stages of degeneration are being explored but the majority of ongoing clinical trials involve adeno-associated viral (AAV) vector-based gene supplementation strategies for select forms of inherited retinal disease. Over 300 genes are associated with inherited retinal degenerations and only a small proportion of these will be suitable for gene replacement therapy. However, while the origins of disease may vary, there are considerable similarities in the physiological changes that occur in the retina. When early therapeutic intervention is not possible and patients suffer loss of photoreceptor cells but maintain remaining layers of cells in the neural retina, there is an opportunity for a universal gene therapy approach that can be applied regardless of the genetic origin of disease. Optogenetic therapy offers such a strategy by aiming to restore vision though the provision of light-sensitive molecules to surviving cell types of the retina that enable light perception through the residual neurons. Here we review the recent progress in attempts to restore visual function to the degenerate retina using optogenetic therapy. We focus on multiple pre-clinical models used in optogenetic strategies, discuss their strengths and limitations, and highlight considerations including vector and transgene designs that have advanced the field into two ongoing clinical trials.

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Section: Human-derived Retinal Organoidsmentioning

confidence: 99%

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

et al. 2020

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“…The above-mentioned technologies that can be used to evaluate and monitor the development and differentiation of ROs have been summarized in Figure 1 . Immunocytochemistry methods have also been used to monitor typical genes such as VSX2 (corresponding to RPCs), HuC/D (corresponding to RGCs), CHAT (corresponding to starburst amacrine cells), Crx (corresponding to PRCs), and RXR (corresponding to cone precursors), aiming to observe and map the progression of differentiation of each human–derived cell type ( Chichagova et al, 2019 ). The improved protocols mentioned in this chapter are summarized in Table 1 .…”

Section: Development Of Retinal Organoidsmentioning

confidence: 99%

Retinal Organoids: Cultivation, Differentiation, and Transplantation

Zhang

Tang³

et al. 2021

Front. Cell. Neurosci.

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Retinal organoids (ROs), which are derived from stem cells, can automatically form three-dimensional laminar structures that include all cell types and the ultrastructure of the retina. Therefore, they are highly similar to the retinal structure in the human body. The development of organoids has been a great technological breakthrough in the fields of transplantation therapy and disease modeling. However, the translation of RO applications into medical practice still has various deficiencies at the current stage, including the long culture process, insufficient yield, and great heterogeneity among ROs produced under different conditions. Nevertheless, many technological breakthroughs have been made in transplanting ROs for treatment of diseases such as retinal degeneration. This review discusses recent advances in the development of ROs, improvements of the culture protocol, and the latest developments in RO replacement therapy techniques.

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“…Völkner et al ( 2016 ) then generated a protocol to generate 3D retinal organoids that do not require the evagination of optic vesicle-like structure, which until then had greatly limited the yield of optic organoids in culture. Chichagova et al ( 2019 ) established a protocol for the development of retinal organoids from hPSCs. These organoids contained all the major retinal cell types and were responsive to light.…”

Section: Current Organoid Culture Strategiesmentioning

confidence: 99%

“…These organoids contained all the major retinal cell types and were responsive to light. The study involved the differentiation of hPSCs into retinal organoids via insulin-like growth factor-1 (IGF-1), retinoic acid and triiodothyronine signaling (Chichagova et al 2019 ).…”

Section: Current Organoid Culture Strategiesmentioning

confidence: 99%

Advances in development and application of human organoids

et al. 2021

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Innumerable studies associated with cellular differentiation, tissue response and disease modeling have been conducted in two-dimensional (2D) culture systems or animal models. This has been invaluable in deciphering the normal and disease states in cell biology; the key shortcomings of it being suitability for translational or clinical correlations. The past decade has seen several major advances in organoid culture technologies and this has enhanced our understanding of mimicking organ reconstruction. The term organoid has generally been used to describe cellular aggregates derived from primary tissues or stem cells that can self-organize into organotypic structures. Organoids mimic the cellular microenvironment of tissues better than 2D cell culture systems and represent the tissue physiology. Human organoids of brain, thyroid, gastrointestinal, lung, cardiac, liver, pancreatic and kidney have been established from various diseases, healthy tissues and from pluripotent stem cells (PSCs). Advances in patient-derived organoid culture further provides a unique perspective from which treatment modalities can be personalized. In this review article, we have discussed the current strategies for establishing various types of organoids of ectodermal, endodermal and mesodermal origin. We have also discussed their applications in modeling human health and diseases (such as cancer, genetic, neurodegenerative and infectious diseases), applications in regenerative medicine and evolutionary studies.

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Differentiation of Retinal Organoids from Human Pluripotent Stem Cells

Cited by 30 publications

References 23 publications

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

Optogenetic Gene Therapy for the Degenerate Retina: Recent Advances

Retinal Organoids: Cultivation, Differentiation, and Transplantation

Advances in development and application of human organoids

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