Researchers publishing in Aging have outlined how biochemical signals derived from created stem cells encourage blood vessels to form new branches in naturally aged mice.
iPSCs, exosomes, and angiogenesis
Exposure to the Yamanaka factors can cause ordinary cells to teturn to early stemness, from which they can divide into any other cell in the body. These are Induced pluripotent stem cells (iPSCs), and they have been studied extensively in aging and other medical research.
Like other cells, iPSCs secrete exosomes, tiny packages of RNA and proteins that serve as signals to other cells. In a previous study, exosomes derived from iPSCs successfully encouraged angiogenesis, the formation of new blood vessels, thus speeding up wound healing [1]. Other experiments have reported positive results in models of heart attack [2].
In this study, the researchers sought to determine if angiogenesis could be encouraged in animals that were suffering from another harmful condition: aging.
Exosomes in life and in the lab
The researchers used a combination of tests in this study. They tested arterial samples (aortic rings) from a total of eight groups of mice: the mice could be either old or young, they could have been pretreated with iPSC exosomes for three months or not, or their aortic rings could have been placed with iPSC exosomes or not.
As expected, the arterial samples of the young mice had much more angiogenesis than the old mice did. Exposing old-mouse samples to iPSC-derived exosomes, either in the living animal or in culture, improved angiogenesis substantially and even more if both approaches were used, showing that these exosomes were consistently effective in this model. Young mice seemed to benefit as well, although not to the level of statistical significance.
Bone marrow cells received similar benefits. The bone marrow cells of old mice proliferated substantially more in culture in all of the treated groups. Interestingly, cells from young mice benefited as well, although much more if the mice had been injected with the exosomes in life.
The senescence-associated biomarkers p53 and p16 were also measured in tissues taken from living animals. Skin, muscle, kidney, lung, spleen, liver and brain tissue all had varying levels of benefit, with the kidneys and muscle being the most affected. The heart seemed unaffected, although p53 and p16 do not substantially differ between the hearts of young and old mice. Antioxidant activity was also improved in most tissues.
Finally, exosomes affected exosomes. The researchers analyzed the serum exosomes of treated old mice and found that they were much more similar to those of young mice than the untreated group’s were.
A potential for treatment?
Exosomes have been studied for some time as a potential method of treating age-related diseases, and this is far from the first paper published on this subject. Because there appear to be none of the other side effects, such as tumors, that can potentially occur with other rejuvenative and regenerative therapies, it might be time to test exosomes in human volunteers for heart diseases and wound healing.
Literature
[1] Qiu, X., Liu, J., Zheng, C., Su, Y., Bao, L., Zhu, B., … & Jin, Y. (2020). Exosomes released from educated mesenchymal stem cells accelerate cutaneous wound healing via promoting angiogenesis. Cell Proliferation, 53(8), e12830.
[2] Balbi, C., & Vassalli, G. (2020). Exosomes: Beyond stem cells for cardiac protection and repair. Stem Cells, 38(11), 1387-1399.
