"Cocktail 3i" against retinopathy
"Primitive" stem cells helped to restore the blood vessels of the eye, preventing blindness in diabetes
Polina Gershberg, Naked Science
Researchers from Johns Hopkins University in the USA were able to use induced stem cells to repair damaged vessels in the retina of diabetic patients. An article about this study is published in Nature Communications (Park et al., Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potential effective revascularization of ischemic retina).
Stem cells obtained by scientists (phosphorescent green) are embedded in the vessels of the iris of mice.
Diabetic retinopathy is one of the most severe complications of diabetes mellitus. This is damage to small blood vessels in the retina of the eye, which can lead to blindness. It is this pathology that is the main cause of vision loss in diabetics. According to researchers, by 2050, about 14.6 million US residents will suffer from diabetic retinopathy.
In the course of their experiments, the scientists obtained induced stem cells from fibroblasts (connective tissue cells) taken from a patient with type I diabetes. According to the researchers, they managed to create structures more primitive than ordinary pluripotent induced human cells (pluripotency is the ability to differentiate into any type of tissue, except for placenta and yolk sac cells). These cells in their potential more closely resembled the cells of the embryo on the sixth day after fertilization.
The researchers used a "3i cocktail" to induce stem cells. It includes three specific inhibitors. These are CHIR9902, which suppresses the activity of GSK3ß kinase and prevents the accumulation of carbohydrates inside the cell, an experimental anti-cancer drug PD0325901, which prevents the growth of cancer cells, and another potential means for the treatment of oncological diseases – a PARP inhibitor.
The picture of survival of vascular precursors in the iris of mice three weeks after injection. On the left is the iris, into which cells obtained by the traditional method were injected, on the right is the retina, into which cells obtained using the "3i cocktail" were injected. The cells that have taken root are shown with red dots. A drawing from an article in Nature Communications.
It turned out that the "cocktail" literally reverses the biological clock of fibroblasts, turning them into an analogue of the cells of the epiblast – the outer layer of the cell wall at one of the early stages of embryo development. In addition, the cells treated with a mixture of inhibitors did not have abnormal epigenetic changes, which is a common problem when receiving induced SC.
The resulting naive cells were then turned into so-called vascular precursors, which were injected into the eyes of mice with diabetic retinopathy. Studies have shown that the structures introduced to rodents migrated to the inner layer of the retina of the eye and took root there more efficiently than vascular cells obtained using traditional approaches.
The work of American scientists may become a breakthrough in the treatment of eye pathologies associated with small retinal vessels, including diabetic retinopathy. "The 3i cocktail for naive reprogramming seems to have erased the epigenetic labels associated with the disease and returned them to a healthy state," comments Professor Elias Zambidis, head of the study. "The results <...> bring us closer to the wider use of stem cells in regenerative medicine without the historical problems that we constantly faced in trying to differentiate cells and not turn them into cancerous ones."
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