Exosomes derived from human amniotic fluid mesenchymal stem cells alleviate cardiac fibrosis via enhancing angiogenesis in vivo and in vitro

Jiajia Hu; Xuliang Chen; Ping Li; Xiaoxu Lu; Jianqin Yan; Huiling Tan; Chengliang Zhang

doi:10.21037/cdt-20-1032

Exosomes derived from human amniotic fluid mesenchymal stem cells alleviate cardiac fibrosis via enhancing angiogenesis in vivo and in vitro

Cardiovasc Diagn Ther. 2021 Apr;11(2):348-361. doi: 10.21037/cdt-20-1032.

Authors

Jiajia Hu¹, Xuliang Chen², Ping Li^{3

4}, Xiaoxu Lu¹, Jianqin Yan¹, Huiling Tan⁵, Chengliang Zhang²

Affiliations

¹ Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
² Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, China.
⁴ Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, China.
⁵ Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Abstract

Background: Cardiac fibrosis is a pathological process characterized by excess extracellular matrix (ECM) deposition and plays a critical role in nearly all types of heart disease. The mechanism of cardiac fibrosis is still unclear and no effective medication treatment of cardiac fibrosis. Research showed that mesenchymal stem cell (MSC) derived exosomes may play a critical role in cardiac fibrosis. The effect of human amniotic fluid MSC (hAFMSC)-derived exosomes (hAFMSCExos) on cardiac fibrosis has remained unclear.

Methods: The hAFMSCExos were extracted using a sequential centrifugation approach. The effects of hAFMSCExos on angiogenesis were analyzed both in human umbilical vein endothelial cells (HUVECs) after oxygen and glucose deprivation (OGD) in vitro, and in isoproterenol (ISO) induced-cardiac fibrosis in vivo.

Results: The hAFMSCExos remarkably up-regulate the motility and migration of HUVECs after OGD compared with phosphate-buffered saline (PBS). Meanwhile, total tube length, total branching points and total loops were significantly raised in HUVECs after OGD treated with hAFMSCExos. The hAFMSCExos alleviated the cardiac fibrosis degree tested by hematoxylin-eosin (H&E) and Masson staining. The protein levels of Collagen I and α-smooth muscle actin (α-SMA) were lower in exosomes group rats than PBS group. Immunofluorescence suggested that hAFMSCExos can promote the expression of CD31 in the rats. Meanwhile, the number of regenerated microvessels was significantly enhanced in rats administrated with exosomes by quantitative analysis of microvessel density. Furthermore, the micro-CT scanning evidenced that hAFMSCExos promote angiogenesis after cardiac fibrosis. The levels of hypoxia-inducible factor 1 α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in the left ventricle accepted HUVECs were higher than PBS treatment at 7 days post-treatment by Western blot analysis.

Conclusions: The hAFMSCExos have proangiogenic effects on endothelial cells and enhanced angiogenesis in cardiac fibrosis. The hAFMSCExos may be a promising potential treatment strategy for cardiac fibrosis.

Keywords: Human amniotic fluid; angiogenesis; cardiac fibrosis; exosome; mesenchymal stem cells (MSCs).