Dedifferentiated fat cell-derived exosomes exhibit similar microRNA expression profiles and biological activities to those of exosomes derived from adipose-derived stem cells

Background Exosomes are extracellular vesicles that assume a significant role in local and systemic intercellular communication. Exosomes secreted by adipose tissue-derived stem cells (ASCs) possess therapeutic potential for various clinical conditions. Dedifferentiated fat cells (DFATs) are mature adipocyte-derived multipotent cells that show phenotypical and functional similarity to ASCs. Although expression profiles of humoral factors in DFATs are very similar to those in ASCs, there is limited knowledge on exosomes derived from DFATs. In this study, we isolated exosomes from the culture supernatant of DFATs and compared the microRNA (miRNA) expression profiles of DFAT-derived exosomes (DFAT-Exo) with those of ASC-derived exosomes (ASC-Exo). Additionally, we assessed the effect of DFAT-Exo administration on proliferation and phenotypic changes of nucleus pulposus (NP) cells and in T lymphocytes in an in vitro setting. Methods Donor-matched DFATs and ASCs were prepared from adipose tissue of three osteoarthritis patients. Exosomes were isolated from the supernatant of both cell types. The global miRNA expression profiles of DFAT-Exo and ASC-Exo were analyzed using miRNA microarrays. Following administration of DFAT-Exo and ASC-Exo, the cell proliferation capability and expression of chondrogenic marker genes in NP cells were evaluated. Flow cytometric analysis was performed to examine the effects of DFAT-Exo and ASC-Exo administration on the anti-CD3/CD28-stimulated proliferation of T cells and on the differentiation of naive T cells into regulatory T cell and Th17 cell subsets. Results Exosomes were successfully isolated from both DFATs and ASCs. MiRNA microarray analysis revealed that the miRNA profiles of DFAT-Exo closely resemble those of ASC-Exo, when compared to fibroblast-derived exosomes. Notably, certain miRNAs specifically expressed in DFAT-Exo were identified. Administration of DFAT-Exo and ASC-Exo promoted cell proliferation and the expression of cartilage-related genes Sox9 and Versican in NP cells. Both DFAT-Exo and ASC-Exo equivalently suppressed anti-CD3/CD28-stimulated proliferation of T cells. Moreover, DFAT-Exo and ASC-Exo exhibited similar capacities to promote the differentiation of naive T cells into regulatory T cell subsets and hinder the differentiation into Th17 cell subsets. Conclusions DFAT-Exo showed comparable miRNA expression profiles and biological activities to those of ASC-Exo. DFAT-Exo may be an alternative attractive tool for exosome-based therapeutic approaches.