Johns Hopkins Medicine scientists say they have successfully turned back the biological hands of time, coaxing adult human cells in the laboratory to revert to a primitive state, and unlocking their potential to replace and repair damage to blood vessels in the retina caused by diabetes. The findings from this experimental study, they say, advance regenerative medicine techniques aimed at reversing the course of diabetic retinopathy and other blinding eye diseases.
Our study results bring us a step closer to using stem cells more widely in regenerative medicine, without the historical problems our field has encountered in getting such cells to differentiate and avoid becoming cancerous." Elias Zambidis, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and a member of Johns Hopkins' Institute for Cell Engineering
Results of experiments using human cells and mice were published online March 5 in Nature Communications .
According to the National Eye Institute, diabetic retinopathy is a leading cause of blindness in U.S. adults. By 2050, researchers estimate that some 14.6 million Americans will have the condition, which results in abnormal blood vessel growth in the retina, where light is processed into vision.
For the study, the scientists began their experiments with a fibroblast -- a connective tissue cell -- taken from a person with type 1 diabetes. Reprogrammed fibroblasts function as "stem" cells, with the potential to give rise to all tissues in the body, including blood vessels.
The Johns Hopkins team, including research associate Tea Soon Park, Ph.D., reprogrammed the fibroblast stem cells to revert to a state that is even more primitive than that of conventional human induced pluripotent stem cells -- more like the state of embryonic cells about six days after fertilization. This is when cells are the most "naive," or more capable of developing into any specialized type of cell with a much higher efficiency than conventional human induced pluripotent stem cells.
To do this, the scientists bathe the cells in a cocktail of nutrients and chemicals. What should go into the cocktail to build a better naive stem cell has been a subject of debate over the past decade.
Zambidis' team used a cocktail mixture of two drugs that other scientists previously used to reprogram stem cells: GSK3β inhibitor CHIR99021, which blocks carbohydrate storage in cells, and MEK inhibitor PD0325901, an experimental anti-cancer drug that can block cancer cell growth. The team had also looked at the potential of a third drug, a PARP inhibitor -- a popular anticancer drug used to treat a variety of cancers including those of the ovaries and breast. Related Stories
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