Characterization of Microfragmented Adipose Tissue Architecture, Mesenchymal Stromal Cell Content and Release of Paracrine Mediators

The use of microfragmented adipose tissue (mu FAT) for the treatment of musculoskeletal disorders, especially osteoarthritis (OA), is gaining popularity, following positive results reported in recent case series and clinical trials. Although these outcomes were postulated to rely on paracrine signals, to date, a thorough fingerprint of released molecules is largely missing. The purpose of this study was to first characterize both structure and cell content of unprocessed lipoaspirate (LA) and mu FAT, and further identify and frame the array of signaling factors in the context of OA disease, by means of high throughput qRT-PCR for extracellular-vesicle (EV) embedded miRNAs and proteomics for tissue and secreted factors. Cell count showed reduction of blood cells in mu FAT, confirmed by histological and flow cytometry analyses, that also showed a conserved presence of structural, endothelial and stromal components and pericytes. In the secretome, 376 and 381 EV-miRNAs in LA and mu FAT, respectively, were identified. In particular, most abundant and mu FAT upregulated EV-miRNAs were mainly recapitulating those already reported as ASC-EVs-specific, with crucial roles in cartilage protection and M2 macrophage polarization, while only a scarce presence of those related to blood cells emerged. Furthermore, secretome proteomic analysis revealed reduction in mu FAT of acute phase factors driving OA progression. Taken together, these results suggest that processing of LA into mu FAT allows for removal of blood elements and maintenance of tissue structure and stromal cell populations, and possibly the increase of OA-protective molecular features. Thus, microfragmentation represents a safe and efficient method for the application of adipose tissue properties in the frame of musculoskeletal disorders.

Automated summary

The use of microfragmented adipose tissue (mu FAT) for the treatment of musculoskeletal disorders, especially osteoarthritis, is gaining popularity. This study characterized the structure and cell content of unprocessed lipoaspirate (LA) and mu FAT, and identified the array of signaling factors in the context of osteoarthritis. The results showed that mu FAT had reduced blood cells and maintained tissue structure and stromal cells, with increased molecular features beneficial for osteoarthritis.