SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema

Eleni Priglinger,Matthias Hackl,Karin Strohmeier,Mario Gimona,Daniela Auer,Martin Barsch,Carolin Lindner,Moritz Weigl,Johannes Grillari,Heinz Redl,Susanne Wolbank,Jaroslaw Jacak,Matthias Sandhofer

doi:10.1038/s41598-020-64215-w

Abstract

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles – but not cCMmiRNAs – were impacted by lipedema. Seven sEVmiRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

Highlights

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria
There are no blood-based parameters to identify lipedema patients so far. Due to this lack of systemic differences, we previously focused on the diseased tissue itself, on the cellular components in which the disease is manifested and analyzed stromal vascular fraction (SVF) cells isolated from liposuction material of lipedema patients
The body mass index (BMI) is similar in lipedema and healthy individuals (p-value 0.39), the standard deviation was similar in healthy and lipedema indicating a comparable distribution within the cohorts

Summary

Introduction

Progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. Patients suffer from pain, reduced joint mobility, hematoma, edema and psychological impacts[2] It was first described in 1940 as a connective tissue disorder, characterized by fluid being collected in the interstitium instead of entering into lymphatics[3]. Besides functioning as an energy storage, white adipose tissue (WAT) responds differentially to physiological and pathological metabolic changes by secreting a large diversity of proteins, hormones, lipids, non-coding ribonucleic acids (RNAs) – including microRNAs (miRNAs) – and extracellular vesicles (EVs)[9,10]. By adipose tissue originate from non-adipocyte cells, such as endothelial and immune cells present in the stromal vascular fraction (SVF) of adipose tissue[9,13]

Objectives

Methods

Results

Conclusion