Dogs have been loyal human companions since their domestication thousands of years ago. With various improvements in veterinary medicine over the past few decades, their life expectancy has increased. However, an unfortunate side effect of this longevity, similar to that in humans, has been an increase in the incidence of chronic and degenerative diseases.
In humans, modern efforts to combat such diseases have led to the development of regenerative therapies, largely based on stem cells. These “baby” cells have the potential to differentiate and mature into many specialized cell types – called “pluripotency”. By transplanting stem cells and directing their differentiation into desired cell types, researchers can effectively regenerate damaged tissue, thereby reversing the course of various complex diseases. Although this technology is being studied extensively in humans, the potential for stem cell therapy in dogs is lacking.
To this end, a team of researchers from Japan, led by Associate Professor Shingo Hatoya of Osaka Prefecture University, worked to isolate “induced pluripotent stem cells” (iPSCs) from dog blood samples. iPSCs are a type of stem cell that can be “programmed” from a developed (or “differentiated”) cell by introducing a specific set of genes into it. These genes code for proteins called “transcription factors” that induce the change from a differentiated to a pluripotent stem cell, which can then mature into different cell types. iPSCs can multiply very quickly and offer a reliable supply of suitable stem cells for regenerative therapies. “We have successfully established an efficient and simple method for generating iPSCs in dogs from mononuclear cells of the peripheral blood,” explains Dr. Hatoya. He stressed the importance of these findings to veterinary science and hoped that “it may be possible to perform regenerative medical treatments on dogs” in the near future. These results were published in the journal Stem Cells and Development.
The previous attempts by these scientists to create iPSCs from canine blood cells using viral “vectors” to deliver the pluripotency-inducing transcription factors have not been as effective as hoped. Therefore, in this study, they tested a different combination of inducing factors that they believe are key to harvesting the full potential of these cells. Above all, the researchers had to control how the reprogrammed cells replicated in the host body. Viral vectors encoding pluripotency-inducing transcription factors can be used to infect blood-derived cells and convert them to iPSCs; However, the researchers had to be careful: because these vectors are integrated into the host genome, re-expression of these pluripotency factors in the host cell can lead to tumor formation when these cells are transplanted into patients. To avoid this, the team developed “footprint-free” stem cells using a specific type of viral vector that can generate iPSCs without genomic insertion and automatically “silenced” via “microRNAs” expressed by the cells. Then they cultured these cells in a special type of media that contained various factors that increased their pluripotency (including a “low molecular weight cocktail”). Indeed, these cells grew and successfully developed germ layers (which form the basis of all organs).
Fascinatingly, these results paved the way for a simple stem cell therapy technique for man’s best friends. “We believe that our method can facilitate research involving disease modeling and regenerative therapies in the veterinary field,” says Dr. Hatoya. Additionally, the authors believe that additional research on regenerative therapies for dogs could have some ripple effects for human medicine. “Dogs share the same environment as humans and spontaneously develop the same diseases, especially genetic diseases.”
Transferring findings from one area to another could mean that veterinarians will be able to find treatments or even cures for some of the diseases that still affect humankind.
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Materials provided by Osaka Prefecture University. Note: The content can be edited by style and length.