A scientific breakthrough has offered new hope in treating blindness and vision loss. Lab-grown cells have restored function in the retina – a layer of light-sensitive cells at the back of the eyeball crucial to sight – in mice.
Duke University researchers pioneer stem cell therapy
Biomedical engineers at Duke University, North Carolina, used induced pluripotent stem cells (iPSCs) to grow specialised blood vessel cells for the first time. When these were injected into mouse models of retinal disease, the ‘retinal endothelial cells’ integrated into the damaged tissue and regenerated blood vessels, restoring retinal function.
The research team also demonstrated the cells’ ability to form functional retinal vascular tissue in a lab-grown environment, which could provide a pathway by which they can model and research various eye diseases.
Potential for treating retinal vascular diseases
The findings, published in the journal Nature Biomedical Engineering, point toward the potential of using the retinal cells and models to develop new methods to treat vision loss and eye disorders, the team says. Study leader Professor Sharon Gerecht said: ‘Retinal vascular diseases affect millions of people, but our understanding remains limited, hindering our ability to discover and develop new therapeutics. Using human stem cells, we generated the cells found in retinal blood vessels, paving the way for new therapeutic approaches.’
Neurons from the retina extend directly to the brain and create the images we see. Similar to the brain, the retina has a blood barrier that controls what goes in and out, including oxygen, nutrients, water, and pharmaceuticals. The barrier is crucial to keep the retina healthy and to provide some protection from diseases. However, Prof Gerecht says it also makes treating the retina difficult.
Challenges in growing retinal cells
She said: ‘This barrier is formed by blood vessel tissue comprising a tight network of retinal endothelial cells, which form the inner layer of blood vessels, in concert with other specialised cells called pericytes and astrocytes. The specificity of these cells and the fact that they do not form in other areas of the body make the complex tissue difficult to heal or to grow from scratch.’
Study first co-author Parker Esswein, a PhD student working in the Gerecht lab, said: ‘When this specialised blood vessel tissue begins to break down, it can cause a lot of different diseases that lead to vision loss. While there are sources of retinal endothelial cells, being able to grow a continuous supply from scratch could offer many advantages for those working in the field.’
Induced pluripotent stem cells as a solution
At present, retinal endothelial cells are collected and grown from real patients – meaning they are expensive with a limited supply. To reduce cost and increase accessibility, the Gerecht lab wanted to see if they could grow them from iPSCs. These are mature adult cells that are reprogrammed to become primal versions of themselves, which can then grow into a variety of other cell types.
The research team took commercial iPSCs and used a well-established procedure to get them to grow into common endothelial cells that form the inner layer of most of the body’s blood vessels. The researchers then used a cocktail of growth factors to get the cells to grow into the specific type of endothelial cells found in the retina.
Lab-grown tissues mimic disease conditions
The team was then able to get the cells to form the same networks and structures that they do within the body. The researchers then subjected the lab-grown tissues to low oxygen and high glucose levels, which are detrimental conditions often seen in real people. These conditions are ‘fundamental’ triggers of diabetic retinopathy – the leading cause of vision loss in working-age people in the United States – and caused the tissue barrier to break down just like it does in patients.
When injected into the mice before any actual vision loss occurred, the cells successfully integrated into the existing tissue and helped develop strong blood vessels with strong barriers.
Future applications and partnerships
Mr Esswein said: ‘The tests showed that these lab-grown cells have promise for preventative treatments, especially since they should be easier and cheaper to obtain using our technique.’ He added: ‘While our benchtop experiments did not attempt to model a wide variety of specific eye diseases in these studies, we’re confident we can create excellent human tissue models in the lab to help better understand these diseases and uncover therapies.’
Now the team is planning to explore potential uses for their retinal endothelial cells both in their laboratory and through emerging industry partnerships. The group also has a patent pending that covers both the stem cell-based therapeutics and in vitro modelling for drug discovery and testing.
