Gene alterations after human adipose-derived stem cell-derived exosome injection in monosodium iodoacetate-induced osteoarthritis rats by microarray analysis

Introduction: Exosome (exo) is a small extracellular vesicles containing cell-derived factors, and serve to mediate the paracrine effect of cells. Despite the therapeutic potential of human adipose-derived stem cells (hADSCs)-derived exo-related treatment modalities, the molecular parameters needed to define the "paracrine effect" remain largely unknown. Material and Methods: Using high-density oligonucleotide RNA sequencing, the differential gene expression profiles between a fraction of exo (derived from hADSCs) and its mesenchymal stem cells subpopulation were obtained. Results: Of particular interest was a subset of 66 genes preferentially expressed at fivefold or higher in the group treated with exo derived from hADSCs. This subset contained numerous genes involved in the angiogenesis, inflammatory response, immune response, cell cycle, cell death, cell differentiation, cell proliferation, DNA repair, RNA splicing, and secretion functions. In addition, six protein networks were constructed. The interaction network consisted of 57 proteins encoded by upregulated genes. However, the interaction network also consisted of 69 proteins encoded by downregulated genes. Discussion and Conclusion: Our results provide a basis for more reproducible and reliable quality control using genotypic analysis for the definition of hADSCs-exo. Therefore, these results will serve to provide a basis for studies of the molecular mechanisms which control the core properties of hADSCs-exo. Understanding the processes driving hADSCs-exo recruitment could prove invaluable in the development of novel, targeted therapies to selectively inhibit pathological responses in OA.