Use of bioreactors for culturing human retinal organoids improves photoreceptor yields

• Published in: Stem cell research & therapy Vol. 9; no. 1; pp. 156 - 14
• Main Authors: Ovando-Roche, Patrick, West, Emma L., Branch, Matthew J., Sampson, Robert D., Fernando, Milan, Munro, Peter, Georgiadis, Anastasios, Rizzi, Matteo, Kloc, Magdalena, Naeem, Arifa, Ribeiro, Joana, Smith, Alexander J., Gonzalez-Cordero, Anai, Ali, Robin R.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 13.06.2018; BioMed Central Ltd; BMC
• Subjects: Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Bioreactors; Bioreactors - standards; Care and treatment; Cell Biology; Cell culture; Cilia; Disease; Drug screening; Electron microscopy; Embryos; Flow cytometry; Genetic aspects; Health aspects; Humans; Immunohistochemistry; Life Sciences; Organoids; Organoids - metabolism; Photoreceptor Cells - metabolism; Photoreceptors; Pluripotency; Pluripotent stem cells; Pluripotent Stem Cells - metabolism; Regenerative Medicine/Tissue Engineering; Retina; Retina - metabolism; Retinal degeneration; Retinal organoids; Scaling; Stem Cells; Transplantation; Retinal organoids; Photoreceptors; Pluripotent stem cells; Bioreactors
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-018-0907-0

Background The use of human pluripotent stem cell-derived retinal cells for cell therapy strategies and disease modelling relies on the ability to obtain healthy and organised retinal tissue in sufficient quantities. Generating such tissue is a lengthy process, often taking over 6 months of cell culture, and current approaches do not always generate large quantities of the major retinal cell types required. Methods We adapted our previously described differentiation protocol to investigate the use of stirred-tank bioreactors. We used immunohistochemistry, flow cytometry and electron microscopy to characterise retinal organoids grown in standard and bioreactor culture conditions. Results Our analysis revealed that the use of bioreactors results in improved laminar stratification as well as an increase in the yield of photoreceptor cells bearing cilia and nascent outer-segment-like structures. Conclusions Bioreactors represent a promising platform for scaling up the manufacture of retinal cells for use in disease modelling, drug screening and cell transplantation studies.