Inflammation‐Stimulated MSC‐Derived Small Extracellular Vesicle miR‐27b‐3p Regulates Macrophages by Targeting CSF‐1 to Promote Temporomandibular Joint Condylar Regeneration

Abstract

Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have been extensively studied in recent years. sEV contents change with the secreting cell state. When MSCs are exposed to an inflammatory environment, they release more functional growth factors, exosomes, and chemokines. Herein, MSCs are stimulated to alter sEV cargos and functions to regulate the inflammatory microenvironment and promote tissue regeneration. Sequencing of sEV miRNAs shows that certain RNAs conducive to cell function are upregulated. In this study, in vitro cell function experiments show that both inflammation‐stimulated adipose‐derived MSC (ADSC)‐derived sEV (IAE) and normal ADSC‐derived sEV (AE) promote cell proliferation; IAE also significantly improves cell migration. Regarding macrophage polarization regulation, IAE significantly promotes M2 macrophage differentiation. RNA‐sequencing analysis indicates that high miR‐27b‐3p expression levels in IAE may regulate macrophages by targeting macrophage colony‐stimulating factor‐1 (CSF‐1). In vivo, a rabbit temporomandibular joint (TMJ) condylar osteochondral defect model shows that both AE and IAE promote TMJ regeneration, with IAE having the most significant therapeutic effect. Therefore, the authors confirm that exposing MSCs to an inflammatory environment can feasibly enhance sEV functions and that modified sEVs achieve better therapeutic effects.

GelMA Hydrogel Loaded with Extracellular Vesicles Derived from Umbilical Cord Mesenchymal Stem Cells for Promoting Cutaneous Diabetic Wound Healing

“…The culture medium was collected and centrifuged according to a previously reported protocol. 23 In brief, the medium was centrifuged at 300 g for 10 min to remove cells, 2000 g for 10 min to remove dead cells, 10 000 g for 30 min to remove cell debris, and 100 000 g for 70 min to remove contaminating proteins. The yielded pellet was washed in PBS at 100 000 g for 70 min to enrich the EVs and then resuspended in PBS.…”

Preparation of Recombinant Human Collagen III Protein Hydrogels with Sustained Release of Extracellular Vesicles for Skin Wound Healing

“…After 14 days, the hydrogel was degraded by about 60% ( Figure 2 F). The membrane surface of EVs has g-acyl group and ε-amine group [ 30 ]. Therefore, TGase could enable EVs to be loaded onto the rhCol III hydrogel, thereby safely and effectively avoiding the sudden release of EVs.…”

Adipose tissue-derived small extracellular vesicles modulate macrophages to improve the homing of adipocyte precursors and endothelial cells in adipose tissue regeneration

“…Previous studies demonstrated macrophages played diverse functions, including scavenging debris ( Peng et al, 2007 ; Wynn and Vannella, 2016 ), recruiting host cells ( Wang et al, 2018 ), promoting vascularization ( Sun et al, 2017 ), and inducing cell differentiation ( Wang et al, 2017 ). Most previous studies focused on the anti-inflammation ability of sEVs to polarize M1 macrophages to M2 macrophages ( Kwak et al, 2022 ; Li et al, 2022 ; Liu et al, 2022 ; Tang et al, 2022 ; Yang et al, 2022 ; Zhao et al, 2022 ). However, the role of macrophages in cell recruitment was largely unknown, especially in the process of tissue regeneration induced by sEVs.…”