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German Stem Cell Scientists Develop 3-D “Mini-retinas” –New Hope for Restoring Sight in Patients with Retinal Degeneration Caused by Diabetes and Inherited Disorders.

Medical breakthroughs using stem cells are aimed at all parts of the body bones, kidneys, joints, spines–and now, sight.

A German study in March in Stem Cell Reports, reports that scientists have created an efficient way of developing 3D retina organoids leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies.

3-D Mini-retinas protocol

The new mini-retina protocol involves cutting an organoid grown from stem cells into three, half-moon shaped pieces at an early stage of eye development. Each of these pieces eventually grows into the full suite of cells found in the retina.

3-D retinal organoids developed in this process efficiently replicate retina formation. This includes the light-detectingATAGLANCE cone cells, which now can be produced in high quantities.

Cone photoreceptors, which are responsible for high acuity and color vision, are the most precious retinal cell type with regard to potential future cell replacement therapies in patients affected by retinal degeneration caused by diabetes and inherited disorders.

The process of developing 3D retinal organoids also allows the surviving organoids to grow to reach sizes similar to uncut organoids. These mini-retinas swim around in the dish and because they’re not attached to a surface, better reflect the structure of retinal tissue during development.

In the past, the inability to produce such cells has been a major limitation for regenerative medicine; however, this new method increases the yield of retinal organoids 4-fold, allowing researchers to take a great step forward in the study of the retina and how to repair it.

3-D Mini-retinas offer more diverse ways to study retina tissue

3-D mini-retinals stem cells“The goal isn’t just to make the closest thing next to a real retina, but also to possibly harness the flexibility of the system to create more diverse ways of studying retina tissue,” says senior author Mike Karl, of the German Center for Neurodegenerative Diseases (DZNE) and part of the Center for Regenerative Therapies (CRTD) at Technische Universität Dresden.

“Even with our new additions to existing organoid systems, we have not yet reached that tipping point of robustness that we need for people without the expertise to grow these models.”

Karl and his colleagues’ comparative studies on pluripotent stem cell-derived human and mouse retina organoids and mouse retina in vivo support the power of the new organoid protocol.

New insights in the study of retinal disease

“Tissue heterogeneity (diversity) is a major challenge in organoid systems, and here our work provides new insight, which will help to develop specific organoid-based models, specifically to reliably study retinal disease mechanism,” says Karl.

The Karl Lab’s change to the mini-retina protocol involves cutting a retina organoid grown from stem cells into three pieces at an early stage of eye development. Each of these pieces, which look like little half moons, eventually grows into the full suite of cells found in the retina, thereby increasing the yield of retinal organoids up to 4-fold compared to previous protocols. Karl’s next objective is to make his 3-D “mini-retinas” even more complex, perhaps by bringing in blood vessels and using the organoids to study regeneration and the function of different neural cell types–specifically, from the human retina.

 

 

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