Duke Engineers Grow Retinal Blood Vessel Cells from iPSCs, Restoring Vision in Mouse Models
核心洞察
Duke University (搜索) biomedical engineers have for the first time grown specialized retinal endothelial cells from induced pluripotent stem cells (iPSCs), published in Nature Biomedical Engineering.
When injected into mouse models of retinal disease, the lab-grown cells integrated into damaged tissue, regenerated blood vessels, and restored retinal function.
The cells successfully formed functional retinal vascular tissue in benchtop experiments and modeled diabetic retinopathy (搜索) when exposed to low oxygen and high glucose conditions.
Biomedical engineers at Duke University (搜索) have achieved a first in regenerative ophthalmology: growing specialized retinal endothelial cells from induced pluripotent stem cells (iPSCs) and demonstrating their ability to integrate into damaged retinal tissue, regenerate blood vessels, and restore function in mouse models. The findings, published online June 30 in the journal Nature Biomedical Engineering, open new avenues for treating retinal vascular diseases (搜索) that affect millions of people in the United States.
"Retinal vascular diseases (搜索) 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 Challenge of the Retinal Blood Barrier
The retina, like the brain, possesses a highly selective blood barrier that strictly regulates the passage of oxygen, nutrients, water, and pharmaceuticals. This barrier is formed by a tight network of retinal endothelial cells working in concert with pericytes and astrocytes. While essential for retinal health, the specificity of these cells — which do not form elsewhere in the body — makes the tissue exceptionally difficult to heal or to grow from scratch.
Currently, retinal endothelial cells are collected and grown from actual patients, a process that is relatively expensive and yields a limited supply. "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 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."
From iPSCs to Specialized Retinal Cells
To overcome supply limitations, Ying-Yu Lin, a former PhD student in Gerecht's lab, and Esswein started with commercial iPSCs and applied a well-established protocol to differentiate them into common endothelial cells — the type that lines most blood vessels in the body. The critical innovation came next: the researchers used a specialized cocktail of growth factors to coax these cells into becoming the specific retinal endothelial cell subtype.
Benchtop Validation and Disease Modeling
The team validated their cells through a series of rigorous experiments. In benchtop assays, the lab-grown cells formed the same networks and structures observed in native retinal tissue. The researchers then subjected these engineered tissues to low oxygen and high glucose levels — conditions that are fundamental causes of diabetic retinopathy (搜索), the leading cause of vision loss in working-age people in the United States. Under these stressors, the tissue barrier broke down just as it does in patients, confirming the model's relevance for disease research.
Therapeutic Promise in Mouse Models
In a critical therapeutic test, the researchers injected their lab-grown retinal endothelial cells into mouse models characterized by weak, unstructured retinal blood vessels. The intervention occurred before any actual vision loss had taken place. The cells successfully integrated into the existing tissue and contributed to the development of strong blood vessels with robust barrier function.
"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."
Future Directions and Commercial Potential
The Gerecht laboratory is now planning to explore the therapeutic and modeling applications of these retinal endothelial cells both internally and through emerging industry partnerships. The group has a patent pending that covers both the stem cell-based therapeutics and the in vitro modeling platform for drug discovery and testing.
The work was supported by the National Institutes of Health (EY035853), 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.