skin stem cell based treatment soon?
Many stem cell therapies have been tested for several years in the search for a cure for degenerative eye diseases. However, these tests are preceded by rigorous screening processes with the risk of endangering patients. In this sense, American researchers have spent nearly 10 years designing organelles that can fully restore the function of retinal cells from reprogrammed skin stem cells. The last step before the clinical trial was to see if the cells of these organelles were able to make proper synaptic connections with the still (healthy) ones from the sick patients. The goal is that the resulting clusters of organelles could replace damaged retinal cells in people suffering from eye degeneration.
In primates, the cells that interact with light and are responsible for “high-precision” vision are cone-shaped located in the fovea. In people with degenerative eye diseases, these cells die, fail to renew themselves, and cause partial or even complete blindness. In a previous study, researchers from the University of Wisconsin-Madison (USA) genetically reprogrammed skin cells to act as stem cells and differentiate functionally into retinal cells similar to foveal cones.
But the biggest challenge in stem cell therapies is the inability to ensure that once they are differentiated in vitro, they behave properly after being implanted in the patient. In 2017, patients actually fell victim to a poorly controlled clinical trial in which fat stem cells were injected directly into their eyes after samples were taken. The results were disastrous, as after being injected, the stem cells differentiated into myofibroblasts, causing retinal detachment and severe intraocular bleeding in three patients.
In new research from the University of Wisconsin-Madison, it took more than a decade to develop the right protocol in the lab to ensure that stem cells properly differentiate into retinal cell organelles. ” We wanted to use cells from these organelles as a reserve for the same type of cells lost in retinal diseases. “, David Gamm, professor of ophthalmology at the University of Wisconsin-Madison, director of the McPherson Eye Research Institute (a laboratory that develops organelles) and co-author of the new study, explains in a press release.
Once this step was accomplished, it was necessary to determine whether the cells would behave properly and communicate with each other after being separated from the compact organelle in order to transmit light signals to the brain. Retinal cells communicate with neurons through synaptic connections. These are small spaces between each axon that carry sensory information between cells.
Cells from the organelles developed by the researchers should therefore have the ability to properly develop the equivalents of these axons and synapses into small functional cords. ” The last piece of the puzzle was to test whether the cords had the ability to connect or bind to other types of retinal cells to communicate. ” says Gamm.
Synaptic connections are established
According to the results reported in the review PNAS, researchers used genetically modified (and neutralized) rabies viruses to identify pairs of cells capable of forming synaptic connections between them. They isolated individual cells from previously compact organelles and gave them a week to develop axons.
Thanks to the fluorescent labeling of the viruses, the researchers could see the connections between the cells as they could be infected by the virus (crossing the synapses). In addition, the researchers were able to confirm that the cells that form the synapses and connections are photoreceptors, similar to the rod-cone cells of the retina.
The next step will now be to see how these cells behave after being implanted in patients. ” All of this ultimately leads to human clinical trials, which is obviously the next step. This step remains delicate, says Gramm. It is important to remember that cells behave differently after implantation and may not perform the expected functions or even cause serious side effects.
