Exosomes Derived From Human Adipose-Derived Stem Cells Inhibit Lipogenesis Involving Hedgehog Signaling Pathway

Ziwan Ji,Shuming Gu,Liqun Li,Yucang He,Chen Ke,Jingping Wang,Zhongming Cai,Qing Wei,Zikai Zhang,Tian Li

doi:10.3389/fbioe.2021.734810

Abstract

Since obesity impairs wound closure and adipose-derived exosomes (ADEs) regulate wound healing in clinical applications, we hypothesized that ADEs may inhibit adipogenesis of adipose-derived stem cells (ADSCs) to reduce the adverse effects of obesity on wound healing. Hedgehog (Hh) signaling has been previously shown to inhibit adipogenesis in ADSCs. The present study aimed to determine the role of ADEs in the adipogenesis of ADSCs and the Hh signaling pathway. ADSCs collected from human adipose tissues were co-cultured with ADEs and treated with an adipogenic inducer. qRT-PCR showed that ADEs could inhibit adipogenic differentiation of ADSCs and activate Hh signaling. The differences in the mRNA expression profiles of genes related to Hh signaling between the groups that were exposed to either high fat or low fat indicated that increased Hh signaling activation is necessary but not sufficient to inhibit adipogenic differentiation in the ADSC differentiation process. The Hh signaling pathway can be activated effectively by ADEs, especially during high-fat exposure after treatment with ADEs. Oil Red O staining of adipocytes suggested that ADEs inhibited not only adipogenic differentiation, but also lipogenesis in ADSCs. Overall, targeted activation of Hh signaling by ADEs reduced lipid accumulation in ADSCs and may be explored for clinical applications.

Highlights

Obesity, characterized by an excess of adipose mass, is a major health problem of the 21st century (Haslam and James, 2005)
The present study aimed to explore the role of adipose-derived exosomes (ADEs) in adipogenic differentiation and lipid accumulation in adipose-derived stem cells (ADSCs) and in the Hh signaling pathway
We revealed that ADEs could inhibit the adipogenic differentiation of ADSCs and that activation of Hh signaling is involved in this process

Summary

Introduction

Obesity, characterized by an excess of adipose mass, is a major health problem of the 21st century (Haslam and James, 2005). Impaired wound closure because of obesity is a complex problem involving many factors. Microenvironment alterations caused by obesity have been reported as a potential contributing factor, as they may lead to a reduced plasticity of adipose-derived stem cells (ADSCs). In 2001, ADSCs were successfully isolated from human fat tissues and were shown to have the potential for adipogenic, osteogenic, and chondrogenic differentiation (PA et al, 2001). ADSCs are an ideal cell type for clinical application owing to their ease of isolation and culture and abundant sources. Because of their self-replication and multidirectional differentiation properties, ADSCs have been successfully used in stem cell therapy strategies for tissue engineering and regenerative

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Conclusion