Research Paper Volume 15, Issue 12 pp 5854—5872

iPSC-derived exosomes promote angiogenesis in naturally aged mice

Xingyu Li1, *, , Heng Zhang1, *, , Xuemeng Wang1, , Meng Lu1, , Qianqian Ding1, , Alex F. Chen1, , Meng Xiang1, , Sifeng Chen1, ,

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
* Equal contribution

Received: March 1, 2023       Accepted: June 6, 2023       Published: June 26, 2023
How to Cite

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


ABTS kit: total antioxidant capability test kit; BMCs: bone marrow cells; BP: biological process; CC: cellular component; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco’s modified Eagle’s medium; exo: exosome; ECM: endothelial cell medium; FBS: fetal bovine serum; GO: Gene Ontology; HUVECs: human umbilical vein endothelial cells; iPSCs: induced pluripotent stem cells; KEGG: Kyoto encyclopedia of genes and genomes; MSCs: mesenchymal stem cells; mLIF: murine leukemia inhibitory factor; MF: molecular function; NTA: nanosight tracking analysis; Oct4: octamer-binding transcription factor 4; ROS: reactive oxygen species; SOX2: sex-determining region Y-box 2; SSEA-1: stage-specific embryonic antigen-1; TAOC: total antioxidant capacity.