iPSC-derived exosomes promote angiogenesis in naturally aged mice

Abstract

Heterochronic parabiosis has shown that aging individuals can be rejuvenated by a youthful circulatory system; however, the underlying mechanisms remain unclear. Here, we evaluated the effect of exosomes isolated from mouse induced pluripotent stem cells (iPSCs) on angiogenesis in naturally aged mice. To achieve this, the angiogenic capacity of aortic ring, the total antioxidant capacity (TAOC), p53 and p16 expression levels of major organs, the proliferation of adherent bone marrow cells, and the function and content of serum exosomes in aged mice administered iPSC-derived exosomes were examined. Additionally, the effect of iPSC-derived exosomes on injured human umbilical vein endothelial cells (HUVECs) was assessed. The angiogenic capacity of aortic rings and clonality of bone marrow cells from young mice were significantly higher than those from aged mice; moreover, the organs of aged mice had a higher expression of aging genes and lower total TAOC. However, in vitro and in vivo experiments showed that the administration of iPSC-derived exosomes significantly improved these parameters in aged mice. The synergistic effect of both in vivo and in vitro treatments of aortic rings with iPSC-derived exosomes improved the angiogenic capacity of aortic rings from aged mice to levels similar to that of young mice. Compared with untreated aged mice, serum exosomal protein content and their promoted effect on endothelial cell proliferation and angiogenesis were significantly higher in untreated young mice and aged mice treated with iPSC-derived exosomes. Overall, these results showed that iPSC-derived exosomes may rejuvenate the body by anti-aging the vascular system.

Isolation of Bovine and Human Milk Extracellular Vesicles

“…Exosomes have an important function in both physiological and pathological processes. On the one side, they induce immunological responses, promote angiogenesis, and improve neurogenesis [12][13][14][15], while on the other hand, they drive the proliferation and migration of cancer cells, contribute to blood-brain barrier damage after a cerebral ischemia, and contribute to pain formation in cancer [15][16][17].…”