November 28, 2021

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Transplantation of cone cells from human stem cells to restore vision

Cell: Transplantation of cone cells derived from human stem cells is expected to restore vision

Cell: Transplantation of cone cells derived from human stem cells is expected to restore vision

 

 

Transplantation of cone cells from human stem cells to restore vision. In a new study, researchers from the United Kingdom, the United States, and Australia found that they used retinal photoreceptor cells (called cones) derived from human stem cells to restore vision in mice with advanced retinal degeneration.

They are now designing a clinical trial to test whether transplanting healthy cone cells to patients with age-related macular degeneration will improve their vision. Related research results were recently published in the journal Cell Reports, with the title of the paper “Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors”.


Other studies have transplanted stem cell-derived retinal cells into patients with macular degeneration, but this latest study in mice transplanted cone cells instead of retinal pigment epithelial cells.

These authors pointed out that they focused on cones because they are most important to human vision. These authors compared the roles of cone cells and rod cells (another type of retinal photoreceptor cell): the former allows people to recognize colors, distinguish other people’s faces, and see things in a bright room, and the latter in dim light. It works and helps peripheral vision. People with degenerated rods may have tunnel vision (a condition where the field of vision becomes narrow), while those with degenerated cones may be completely blind.

The most common eye disease associated with cone degeneration is macular degeneration. If people live to a sufficiently old age, then they will have some form of macular degeneration. Ophthalmologists can sometimes slow down the development of this disease, but so far they have not been able to reverse visual decline.

These authors want to know whether stem cells differentiated into cones can restore vision to a certain extent in mice with inactive cones. They developed two variants of human cone cells: one is derived from embryonic stem cells and has normal function and appearance; the other is a control type, which has a normal appearance but cannot respond to light. These control cones were derived from the peripheral blood of a 40-year-old patient with achromatopsia, which causes partial or complete loss of color vision.

These authors transplanted these cone cells into the retina of mice that had been bred with advanced eye disease and had completely non-functional cone cells. The purpose of using these mice is to eliminate the residual function of existing cone cells, rather than newly transplanted cone cells, which may cause visual improvement. In order to ensure that these mice will not launch immune defenses against human cells, they also have immunodeficiency after breeding.

The authors injected functional cones into the retinas of 32 mice, and injected abnormal cones into the other 23 eyes. Sometimes mice have both eyes transplanted, sometimes only one eye. These two types of cone cells, whether functional or not, are attached to the retina to form a cell cluster. This is a typical feature of a healthy eye and a necessary condition for seeing things under strong light.

 

But once the authors exposed the mice to light, the similarities ended. In an eye test called microelectroretinogram designed to measure this, the retinas of mice with functional human cones respond to light, while those with non-functional cones The retina of the mouse did not respond to light. In another test, mice that received functional cone cell transplantation chose to retreat to a dark room under selective circumstances, indicating that these nocturnal animals felt the light and avoided the light as they usually do . In contrast, mice with non-functional cones stayed in the light most of the time.

These authors stated that it took them twenty years to truly achieve the purpose of this research. This proof-of-concept study shows that transplanted functional cones can improve vision. Although they do not currently have the ability to produce cones on a large scale, these authors believe that they can produce enough cones for human clinical trials. Their next step is to recruit 16 participants in the UK in the next few years.

Sai Chavala, an ophthalmologist at the University of North Texas Health Sciences Center in the United States, pointed out that one concern of stem cell transplantation is that it takes some time for stem cells to mature into cells for transplantation. In a previous study in 2020, Chavala and colleagues have discovered that it is possible to directly transform mouse skin cells into photoreceptor cells that can be transplanted into the mouse retina without first converting the skin cells into inducible cells. Pluripotent stem cells (Nature, 2020, doi:10.1038/s41586-020-2201-4). However, mouse skin cells are directly transformed into rod cells instead of cone cells.

 

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