Mesenchymal stem cell-derived exosomal miR-223 regulates neuronal cell apoptosis

Hong Wei,Yuhao Xu,Hui Chen,Xiaolan Zhu,Yuefeng Li,Qi Chen

doi:10.1038/s41419-020-2490-4

Abstract

Hypoxia limits the survival and function of neurons in the development of Alzheimer’s diseases. Exosome-dependent intercellular communication is an emerging signaling mechanism involved in tissue repair and regeneration; however, the effect and underlying mechanism of mesenchymal stem cell-derived exosomes in regulating neuronal cell apoptosis have not been determined. Here, we showed that the establishment of an AD cell model was accompanied by increased HIF-1α expression and cell apoptosis, impaired cell migration, and decreased miR-223. MSC-derived exosomes were internalized by the AD cell coculture model in a time-dependent manner, resulting in reduced cell apoptosis, enhanced cell migration and increased miR-223, and these effects were reversed by KC7F2, a hypoxic inhibitor. Furthermore, MSC-derived exosomal miR-223 inhibited the apoptosis of neurons in vitro by targeting PTEN, thus activating the PI3K/Akt pathway. In addition, exosomes isolated from the serum of AD patients promoted cell apoptosis. In short, our study showed that MSC-derived exosomal miR-223 protected neuronal cells from apoptosis through the PTEN-PI3K/Akt pathway and provided a potential therapeutic approach for AD.

Highlights

Alzheimer’s diseases (AD) is an irreversible neurodegenerative disease with complex pathogenesis, affecting 47 million people worldwide[1]
Model for the role of Mesenchymal stem cell (MSC)-derived exosomal miR-223 in the regulation of neuronal cell apoptosis was shown in the additional file 5. These results indicated that MSCderived exosomal miR-223 may inhibit neuronal apoptosis through the PTEN-PI3K/Akt pathway
With the cerebral hypoxic milieu being a potential feature and an irreversible factor of AD, understanding the multiple interactions between hypoxia and impaired nerve cells is of paramount significance[25]

Summary

Introduction

Alzheimer’s diseases (AD) is an irreversible neurodegenerative disease with complex pathogenesis, affecting 47 million people worldwide[1]. The high mortality of patients with AD is mainly ascribed to the complex aetiology and limited therapeutic interventions. In the past few years, based on the abnormal aggregation of Aβ, researchers have attempted to find methods to inhibit the aggregation and spread of Aβ protein or to promote its clearance[2]. These drug candidates failed to reverse AD or delay progression.

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