Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines

Abstract

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.

Hyaluronic acid: An overlooked extracellular vesicle contaminant

“…Therefore, it is possible that coisolated HA contaminants may contribute to immunomodulatory effects observed with cancer cell-derived EVs (Marar et al, 2021). Alternatively, it could be speculated that anti-inflammatory effects observed in numerous studies with mesenchymal stromal cell (MSC)-derived EVs (Cruz et al, 2015;Seo et al, 2019;Tian et al, 2020;Wang et al, 2019Wang et al, , 2021) may be partially attributed to co-isolated HA contaminants. For example, MSC-derived EVs reduce inflammation in standard in vitro and in vivo assays, such as those based on macrophage responses to lipopolysaccharide (LPS) (Pacienza et al, 2019), a Toll-like receptor 4 (TLR4) ligand.…”

“…Samples were processed using a KrosFlo KR2i TFF System (Repligen), as previously described (Busatto et al, 2018(Busatto et al, , 2020(Busatto et al, , 2021Tian et al, 2020;Wang et al, 2021). Briefly, samples (0.2-0.8 L of 300 ng/mL HA solution or conditioned cell culture medium) were filtered using sterile hollow fibre modified polyethersulfone membranes with 0.65 µm (Spectrum Labs, D02-E65U-07-S) and 750 kDa (Spectrum Labs, D02-E750-05-S) molecular weight cut-off pores to remove any remaining cell debris and small biomolecules, respectively.…”

Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice

“…[109,110] EV Characterization: The size distribution and particle concentration of reconstituted PEV were characterized with NTA, as described previously. [113,124] PEV was reconstituted and diluted 1:100 in PBS and analyzed with a Nanosight NS300 V3.3.4 (Malvern Panalytical, Malvern, UK), using the following measurement settings: three replicates with measurement time at 60 s, flow rate 40 μL min −1 , camera level 11, and detection threshold 4.…”

Extracellular Vesicle and Lipoprotein Interactions

“… ,,,, As nanoparticles move through various compartments in the body (for example, the blood, tissue interstitium, intracellular space) the biomolecular corona changes and evolves to reflect the surrounding environment . Notably, Apo are common biomolecular corona components of both synthetic nanoparticles and EVs. ,,,, In addition to being present in the blood, Apo and lipoproteins can be found in the interstitial space and intracellularly, suggesting that Apo may be key components of nanoparticle coronas in several microenvironments.…”