Retinal Organoids - Newcells

Retinal platform

An in vitro, light responsive, retinal model for accurate predictions of in vivo outcomes you can have confidence in.

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Retinal Organoids

An in vitro, light responsive retinal model for accurate predictions of in vivo outcomes you can have confidence in. 

The retinal organoids model from Newcells recapitulates the complex structure of the retina.

Retinal Organoid Product description

Retinal organoids and RPEs from multiple species. 

Cone photoreceptors in retinal organoids
Cone photoreceptor cells labelled with anti-Opsin (Red/Green) antibody at 150 days of differentiation.
Format 10 organoids per 5ml microfuge tube 
150 ml of optimized cell culture medium per 100 organoids 
2 x 96 well plates per 100 organoids 
2 x Pasteur pipettes 
Cell Types Organoids 
Rod and Cone photoreceptors 
Retinal ganglion cells (RGCs) 
Bipolar cells 
Horizontal cells 
Amacrine cells 
Müller glial cells 
 
RPE (expected availability 2022) 
Retinal pigment epithelial cells
Species Human 
Rat (In development) 
Non-human primate (In development) 
Available analytical readouts  Immunofluorescence analyses 
Gene expression by RT-qPCR 
Transcriptomic analysis by single-cell RNA sequencing 
Cytotoxicity assays 
Cytokine release 
Flow cytometry 
Electron microscopy 
Custom assays 
Origin Heathy donor 
Patient samples 
Assay Window  ≥30 days  

Retinal Organoid Characterization

Gene expression through different stages

Differentiation follows the developmental timeline of embryonic development of the retina with various cell types arising at different times in a sequential manner. Long-term cell survival is hauled by the limitations of the in vitro culture conditions and the limitations of the model itself. (e.g. absence of visual cortex).

Expected protein expression at d150 and d180

* Small number of developing rods and cones
** Expressed at transcriptional level

Characterization of iPSC-derived Retinal Organoids

Photoreceptors and Retinal Ganglion Cells in retinal organoids
Localization and distribution of photoreceptors (RCVRN, green) and retinal ganglion cells (SNCG, red) in retinal organoids at d150.
Cone photoreceptors and amacrine cells in retinal organoids
Representative IF image of retinal organoid at d210. (A) Localisation and distribution of cone photoreceptors (OPN1MW/LW, green) and amacrine cells (AP-2α, red); (B) detailed view of image A, showing cone photoreceptors with primitive outer segments
Muller glia cells in retinal organoids
Localization and distribution of Müller glia cells (CRALBP, red) in retinal organoids at d180.
Amacrine cells in retinal organoids
Localization and distribution of amacrine cells (AP-2α, red) in retinal organoids at d150.
Horizontal cells in retinal organoids
Localization and distribution of horizontal cells (PROX1, green) in retinal organoids at d150

Retinal Platform

Newcells retinal organoids and retinal pigment epithelium (RPE) are developed from ethically sourced healthy donors and patients iPSCs (Induced Pluripotent Stem Cells). The process follows the developmental timeline of retinogenesis in vivo and takes approximately 6-8 months. The 3D cultures are monitored throughout the differentiation and assessed using fluorescent staining for key cell-specific markers.

Fluorescent labelled cells in retinal organoids
Fluorescent labelled cells of iPSC-derived retinal organoids  

Characteristics of iPSC-derived retinal organoids and RPE

  1. The organoids are ~ 1.3 mm in diameter and contain ~40,000 cells.
  2. Contain all major retinal cell types and recapitulate the architecture of the human retina
  3. Fully Stratified
  4. Formation of primitive photoreceptor outer segments leading to responsiveness to light
  5. All cell layers allows drug permeation
  6. The organoids respond to known toxins similar to that seen in vivo

This in vitro retinal platform is unique for disease modelling and investigational drug safety and efficacy: 

  • Recapitulates human retinal architecture 
  • Mimics in vivo physiological features such as responses to light (1) and known toxins  
  • Tested for different applications, including gene therapy, toxicology, and retinal disease modelling
  • On demand supply through regular batch release every 4-6 weeks  
  • Bespoke projects in our state-of-the-art UK facilities 

Light response of the Retinal Organoids 

Retinal Organoids light response
Light-driven spiking activity recorded from presumed ON-Centre retinal ganglion cells (RGCs) and OFF-Centre RGCs. In the raster plot, each small vertical bar indicates the time stamp of a spike, where each row represents a different RGC. The left half illustrates the activity before stimulus onset and separated by the red line, the right half the activity when exposed to light. 

References for this page
Hallam, D. et al. “Human-Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient-Dependent Efficiency.” Stem cells (Dayton, Ohio) vol. 36,10 (2018): 1535-1551. doi:10.1002/stem.2883

  
Chichagova, V. et al.. Cellular regeneration strategies for macular degeneration: past, present and future. Eye (Lond). 2018;32(5):946-971

 
Chichagova V. et al., . Differentiation of Retinal Organoids from Human Pluripotent Stem Cells. Curr Protoc Stem Cell Biol. 2019 Sep;50(1):e95. doi: 10.1002/cpsc.95. PMID: 31479596.


Chichagova, et al. “Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent.” Stem cells (Dayton, Ohio) vol. 38,2 (2020): 195-201. doi:10.1002/stem.3116  

Newcells Retinal Organoid Model 

Accelerate your research with a reliable and consistent, light responsive model of healthy and diseased retinal tissue.

Using organoids could significantly reduce or in some cases eliminate the requirement for animal experiments.

  1. Recapitulates the human retinal architecture and responds to known toxins similar to in vivo models 
  2. Allows modelling of patient specific inherited retinal diseases 
  3. Tested for applications in disease modelling, gene therapy and toxicity

Pricing

RESOURCES:  

Application of organoid technology for retinal disease modelling and drug discovery; Chichagova, Drug Target Review, June 2020 
Application of organoid technology for retinal disease modelling and drug discovery (drugtargetreview.com) 

Human iPSCs generate a light responsive retinal organoid with variable and nutrient dependent efficiency; Hallam et al, Stem Cells, 2018, 36(10), 1535-1551 
Human-Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient-Dependent Efficiency – PubMed (nih.gov) 

Room temperature shipment does not affect the biological activity of iPSC derived retinal organoids; Georgiou et al, PLOS One, 15(6), e0233860 
Room temperature shipment does not affect the biological activity of pluripotent stem cell-derived retinal organoids (plos.org) 

Enhancing immune function of hiPSC derived retinal organoids by incorporating microglial cells; Chichagova et al, Investigtive Ophthamology and VISUAL Science, 2020, 61(7) 
Enhancing immune function of hiPSC-derived retinal organoids by incorporating microglial cells | IOVS | ARVO Journals 

Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line and method dependent; Chichagova et al, Stem Cells, 2020, 38(2), 195-201 
Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent – PubMed (nih.gov) 

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