Summary: Retinal vascular diseases, including diabetic retinopathy, impact millions of people and stand as a primary cause of blindness. Because the retina is technically an extension of the central nervous system, it is shielded by a highly selective blood-retina barrier that filters what can enter or leave eye tissue.
This barrier is formed by an intricate, localized inner layer of specialized retinal endothelial cells working alongside pericytes and astrocytes. Because these exact cells do not develop anywhere else in the body, sourcing a reliable supply to model diseases or heal tissue from scratch has been a long-standing, expensive, and supply-limited bottleneck for biomedical engineering.
In a new study, researchers successfully grew highly specialized retinal endothelial cells from induced pluripotent stem cells (iPSCs) for the first time. The team developed a custom growth-factor cocktail that successfully coaxed standard stem cells into mimicking the exact physiological behavior of eye vasculature. When injected into animal models of retinal disease, these lab-grown cells seamlessly integrated into the damaged tissue, completely regenerating degraded blood vessels, fortifying the blood-retina barrier, and fully restoring retinal function.
Key Facts
- The iPSC Reprogramming Paradigm: Rather than harvesting scarce, expensive, and highly variable endothelial cells directly from human tissue donors, the team utilized adult cells reprogrammed back into their primal stem cell state (iPSCs) to generate an infinite, standardized supply.
- The Growth Factor Cocktail: To achieve this, researchers first grew the iPSCs into common vascular endothelial cells. They then deployed a specialized, targeted cocktail of biochemical growth factors to permanently guide them into becoming the ultra-specific endothelial cells unique to the retina.
- Replicating Diabetic Retinopathy: On the laboratory benchtop, scientists successfully forced these new tissues to organize into functional vessel networks. When exposed to low-oxygen (hypoxia) and high-glucose states, the lab-grown networks broke down identically to how diabetic retinopathy degrades blood vessels in real human patients, creating a perfect drug-discovery testing platform.
- Preventative Vivo Integration: When injected into mouse models exhibiting weak, unstructured retinal vessels, the iPSC-derived cells successfully navigated to the site of damage, incorporated themselves into the existing host matrix, and constructed robust blood vessels with fortified barriers before vision loss could take hold.
- Commercialization & Patent Status: Backed by these dual in vitro modeling and in vivo therapeutic milestones, Duke University has a patent pending covering both the stem cell-based cellular therapeutics and the specialized platform for automated drug testing.
Source: Duke University
Biomedical engineers at Duke University have used induced pluripotent stem cells (iPSCs) to grow specialized blood vessel cells critical to retinal health for the first time.
When injected into mouse models of retinal disease, these “retinal endothelial cells” integrated into the damaged tissue to regenerate blood vessels and restore retinal function. Researchers also demonstrated these cells’ ability to form functional retinal vascular tissue in a lab-grown environment, providing a pathway to model and research various eye diseases.
The results, published online June 30 in the journal Nature Biomedical Engineering and federally funded through the National Eye Institute and NASA, point toward the potential of using these retinal cells and models to develop new methods of impactful vision loss treatments and eye disorder research.
“Retinal vascular diseases affect millions of people in the US, but our understanding remains limited, hindering our ability to discover and develop new therapeutics,” said Sharon Gerecht, the Paul M. Gross Distinguished Professor and Chair of Biomedical Engineering at Duke. “Using human stem cells, we generated the cells found in retinal blood vessels, paving the way for new therapeutic approaches.”
The old saying that the eyes are windows into the soul is more accurate than one might think. Neurons from the retina—the back part of the eye that detects light—extend directly to the brain, technically making the eyes part of the central nervous system.
Also like the brain, the retina has a blood barrier that strictly controls what gets in and out such as oxygen, nutrients, water—and pharmaceuticals. While this barrier keeps the retina healthy and relatively protected from disease-causing agents, it also makes treating the retina difficult.
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 specialized 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.
“When this specialized blood vessel tissue begins to break down, it can cause a lot of different diseases that lead to vision loss,” said Parker Esswein, a PhD student working in the Gerecht laboratory and first co-author of the paper. “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.”
These retinal endothelial cells are currently collected and grown from real patients, making them relatively expensive with a limited supply. To expand access, reduce cost and control variability, the Gerecht lab wanted to see if they could grow them from iPSCs. These are essentially mature adult cells reprogrammed to become primal versions of themselves that can then grow into a wide variety of other cell types.
To do this, Ying-Yu Lin, a former PhD student in Gerecht’s lab, and Esswein 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 specialized cocktail of growth factors to coax the cells into becoming the specific type of endothelial cells found in the retina.
Once successful, the researchers put their new creations to the test.
In benchtop experiments, the team was able to get the cells to form the same networks and structures that they do within the body. They then subjected these lab-grown tissues to low oxygen and high glucose levels, which are detrimental conditions often seen within real people. These conditions are fundamental causes 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.
The researchers then tried their lab-grown cells as a therapy for mouse models with weak, unstructured retinal blood vessels. When injected into the mice before any actual vision loss occurred, these cells successfully integrated into the existing tissue and helped develop strong blood vessels with strong barriers.
“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,” Esswein said. “And 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.”
Moving forward, the researchers are planning to explore these 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 modeling for drug discovery and testing.
Funding: This work was supported by the National Institutes of Health (EY035853), the SNT0101 from the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A, the National Science Foundation Research Fellowship Program, and the National Defense Science & Engineering Graduate Fellowship Program.
Key Questions Answered:
A: The eyes are actually an outpost of your central nervous system, your retinal neurons connect directly to your brain. Because of this, the retina features a fiercely protected blood barrier, formed by a tightly woven inner lining of ultra-specialized retinal endothelial cells. These cells act as strict security guards, controlling exactly what nutrients get in and keeping harmful materials out. Because these cells are uniquely adapted to the high-stakes environment of the eye, they don’t form anywhere else in the body and are incredibly difficult to source, study, or heal once they begin to break down.
A: The researchers used induced pluripotent stem cells (iPSCs), which are mature adult cells reprogrammed back into a blank-slate state. First, they used a standard chemical recipe to turn these stem cells into ordinary endothelial cells—the kind that line basic blood vessels throughout your body. Then came the breakthrough: they exposed these generic cells to a highly specialized, custom cocktail of biochemical growth factors. This specific recipe acted like a chemical roadmap, coaxing and forcing the generic cells to specialize further until they transformed into the rare, tight-binding endothelial cells exclusive to the retina.
A: This technology hits a home run on two fronts. First, as a testing tool, scientists can grow these eye vessels in a dish and subject them to high-glucose and low-oxygen conditions. This perfectly mirrors diabetic retinopathy, allowing researchers to watch eye disease destroy tissue in real time and test new drugs safely on human cells. Second, as a cure, the team injected these lab-grown cells into mice with failing eye vasculature. The new cells actually migrated straight into the damaged areas, integrated perfectly with the host tissue, and rebuilt strong, healthy blood vessels, proving they can act as a preventative cellular therapy to stop vision loss before it even starts.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and visual neuroscience research news
Author: Ken Kingery
Source: Duke University
Contact: Ken Kingery – Duke University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modeling” by Ying-Yu Lin, Parker Esswein, Lucas Ramirez, Emily Warren, Julian Nicenboim & Sharon Gerecht. Nature Biomedical Engineering
DOI:10.1038/s41551-026-01712-9
Abstract
Derivation of functional retinal endothelial cells from human pluripotent stem cells for therapeutics and modeling
Retinal microvascular diseases involve a compromised inner blood–retina barrier (iBRB), which remains poorly understood. A renewable source of human iBRB endothelium is thus vital for advancing eye research and treatment development.
Here we differentiated human induced pluripotent stem cells into retinal endothelial cells (iRECs) via the Wnt–β-catenin pathway, namely Norrin–Frizzled4 signalling. These iRECs show genetic, protein and functional fidelity as well as unique retinal features.
When injected into oxygen-induced retinopathy mice, iRECs integrated into the host vascular network and revascularized the ischaemic eye, rescuing the tissue. In microphysiological models, iRECs form perfusable microvascular networks that recapitulate iBRB morphology and phenotype in both healthy and diabetic states while also physiologically organizing and interacting with induced pluripotent stem cell-derived retinal pericytes.
Our study establishes functional human iRECs and microphysiological iBRB models that facilitate mechanistic studies aimed at identifying therapeutic targets and promoting the revascularization of injured retinas, thereby supporting treatment advancement.
