Abstract

Transplantation of mesenchymal stem cells has been considered as an auspicious treatment for repairing nerve injuries. The rat adrenal pheochromocytoma cell line (PC12) is one of the traditional models for the study of neuronal differentiation and neuroregeneration in vitro. However, the effects of adipose mesenchymal stem cell-derived exosomes (ADSC-exo) on PC12 cells remain unclear and to be elucidated. In our study, the effects of ADSC-exo on PC12 cells were investigated. ADSC-exo were isolated by ultracentrifugation and characterized by transmission electron microscopy, flow nanoanalysis, and western blot. The effects of ADSC-exo on PC12 cell proliferation, migration, apoptosis, and the protein levels were analyzed using CCK-8 assay and EdU incorporation assay, transwell migration assay and scratch wound assay, flow cytometry, and western blot, respectively. We successfully isolated and purified exosomes from ADSC supernatant and found that ADSC-exo treatment significantly promoted PC12 cell proliferation and migration, inhibited their apoptosis, and activated the PI3K/AKT pathway, while PI3K/AKT signaling repression using LY294002 exhibited the opposite effects. The results showed that ADSC-exo promoted proliferation and migration and inhibited apoptosis of PC12 through the activation of the PI3K/AKT pathway. Thus, the effect of ADSC-exo on PC12 cells may suggest ADSC-exo may be a promising therapeutic for nerve damage.

Highlights

  • Radical pelvic surgery, such as that performed for cervical cancer and ovarian cancer, often leads to dysfunction in urination

  • Adipose mesenchymal stem cells (ADSCs) are one kind of MSCs derived from adipose tissue, and they have the capacity for self-renewal and differentiation into adipocytes, osteoblasts, chondrocytes, and nerve cells [8]

  • The primary ADSCs adhered to the wall and grew in a spindle shape

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Summary

Introduction

Radical pelvic surgery, such as that performed for cervical cancer and ovarian cancer, often leads to dysfunction in urination. This may be related to pelvic plexus nerve injury caused by surgery [1,2,3]. Recent studies have confirmed that mesenchymal stem cells (MSCs) can promote repair of nerve injury and improvement of function [4,5,6,7]. Adipose mesenchymal stem cells (ADSCs) are one kind of MSCs derived from adipose tissue, and they have the capacity for self-renewal and differentiation into adipocytes, osteoblasts, chondrocytes, and nerve cells [8]. A growing body of research has shown that the therapeutic effect of ADSCs may not depend on its multidirectional differentiation and is more likely to be related to the cytokines or exosomes secreted by cells [9,10,11]

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