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

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.

MiR‐24‐3p regulates the differentiation of adipose‐derived stem cells toward pericytes and promotes fat grafting vascularization

“…Characterization and trilineage differentiation of ADSCs were performed as previously described 24 . The expression of CD29, CD31, CD44, CD45, and CD90 was detected using rabbit anti‐human CD29, CD31, CD44, CD45, and CD90 monoclonal antibodies (1:100; Abcam, Cambridge, UK), followed by goat anti‐rabbit immunoglobulin G conjugated with fluorescein isothiocyanate (Abcam).…”

“…ADSCs were isolated and cultured as previously described. 24 ADSCs were isolated from adipose tissue obtained from non-obese individuals (BMI < 25 kg/m 2 ; n = 5) undergoing liposuction. Oil components and blood layers were discarded.…”

“…The trilineage differentiation potential of adiposederived mesenchymal stem cells was assessed as previously described. 24 All chemicals were purchased from Oricell. Osteogenic differentiation was induced by incubating adipose-derived mesenchymal stem cells in culture medium supplemented with 10 mM βglycerophosphate, 50 μM ascorbic acid, and 0.1 μM dexamethasone.…”

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

“…However, the use of ADSCs for the treatment of obesity-related disorders could not be limited to chronic wounds. In fact, ADSC-derived exosomes have been shown to inhibit both adipogenic differentiation and lipogenesis in ADSCs through activation of the Hedgehog (Hh) pathway [ 165 , 166 ]. Despite the promising results achieved with MSCs in the treatment of diabetes and its associated comorbidities, clinical data on the efficacy of autologous ADSCs are still lacking [ 167 , 168 ].…”

The emerging roles and mechanisms of exosomal non-coding RNAs in the mutual regulation between adipose tissue and other related tissues in obesity and metabolic diseases

“…In addition, adipocyte EXs can promote the adipogenic differentiation of mouse stromal preadipocytes OP9 through TRPML1 ( 93 ). In addition, treatment with ADEXs can effectively activate the hedgehog (Hh) signaling pathway, especially during the HFD exposure, and inhibits both adipogenic differentiation and lipogenesis in ADSCs ( 94 ).…”