Journal Article

Exosomes Derived from Akt‐Modified Human Umbilical Cord Mesenchymal Stem Cells Improve Cardiac Regeneration and Promote Angiogenesis via Activating Platelet‐Derived Growth Factor D

Sun, Xiaoxian, Sun, Li, Zhu, Wei, Zhao, Xiaosu, Xu, Wenrong, Sun, Xiaochun, Zhao, Yuanyuan, Qian, Hui, Ma, Jie

2017

Overview

We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well known that the activation of Akt is involved in stem cell‐induced cardioprotection. In the present study, we investigated whether exosomes released from Akt‐overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt‐hucMSCs) by using an adenovirus transfection system. Exosomes were isolated from control hucMSCs (Exo) and Akt‐hucMSCs (Akt‐Exo). An acute myocardial infarction model was created by ligation of the left anterior decedent coronary artery (LAD) in rats. Various source exosomes (400 µg of protein) were infused via the tail vein immediately after LAD ligation. The cardiac function was evaluated by using echocardiography after different treatments for 1 and 5 weeks, respectively. Endothelial cell proliferation, migration, and tube‐like structure formation, as well as chick allantoic membrane assay, were used to evaluate the angiogenetic effects of Akt‐Exo. The results indicated that cardiac function was significantly improved in the animals treated with Akt‐Exo. In addition, Akt‐Exo significantly accelerated endothelial cell proliferation and migration, tube‐like structure formation in vitro, and blood vessel formation in vivo. The expression of platelet‐derived growth factor D (PDGF‐D) was significantly upregulated in Akt‐Exo. However, the angiogenesis was abrogated in endothelial cells treated with the exosomes obtained from MSCs transfected with PDGF‐D‐siRNA. Our studies suggest that exosomes obtained from Akt‐modified hucMSCs are more effective in myocardial infarction therapy through promoting angiogenesis. PDGF‐D plays an important role in Akt‐Exo‐mediated angiogenesis. Stem Cells Translational Medicine 2017;6:51–59

• Publisher: Oxford University Press,John Wiley and Sons Inc
• Subject: Adenoviruses / Akt / AKT protein / Angiogenesis / Animals / Apoptosis / Blood platelets / Cardiac function / Cardioprotection / Cell growth / Cell Line / Cell migration / Cell Movement / Cell Proliferation / Chickens / Coronary artery / Coronary vessels / Cytokines / Data analysis / Echocardiography / Efficiency / Endothelial cells / Endothelial Cells - cytology / Exosomes / Exosomes - metabolism / Growth factors / Heart / Heart - drug effects / Heart - physiology / Heart attacks / Humans / Kinases / Lymphokines - metabolism / Mesenchymal stem cells / Mesenchymal Stem Cells - cytology / Mesenchymal Stem Cells - drug effects / Mesenchymal Stem Cells - metabolism / Mesenchyme / Myocardial infarction / Myocardium - pathology / Neovascularization, Physiologic / Platelet-derived growth factor / Platelet-Derived Growth Factor - metabolism / Platelets / Platelet‐derived growth factor D / Proteins / Proto-Oncogene Proteins c-akt - metabolism / Rats, Sprague-Dawley / Receptors, Platelet-Derived Growth Factor - metabolism / Regeneration / siRNA / Stem cell transplantation / Stem cells / Studies / Tissue‐Specific Progenitor and Stem Cells / Transfection / Translational s and Reviews / Umbilical cord / Umbilical Cord - cytology / Veins & arteries / Wound Healing