Therapeutic Potential of Feline Adipose-Derived Stem Cell Exosomes in the Treatment of Feline Idiopathic Cystitis: A Characterization and Functional Analysis of miRNA Content.

Abstract

Feline Idiopathic Cystitis (FIC), is a chronic lower urinary tract condition in cats analogous to PBS/IC in women, which presents significant treatment challenges due to its idiopathic nature. Recent advancements in regenerative medicine highlight the potential of Adipose Tissue-Derived Stem Cells (ADSCs), particularly through their secretome, which includes mediators, bioactive molecules, and extracellular vesicles (EVs). Notably, exosomes, a subset of EVs, facilitate cell-to-cell communication and, when derived from ADSCs, exhibit anti-inflammatory properties and contribute to tissue regeneration. In this work, we aim to characterize the content of exosomes derived from feline ADSCs (fADSCs) to elucidate their mechanisms of action on recipient cells and assess their therapeutic potential for FIC. Exosomes were isolated from fADSCs and their microRNA (miRNA) content sequenced using Illumina technology. Our findings demonstrate that fADSC-derived exosomes harbor miRNAs that can induce regenerative processes, such as cell proliferation, immune modulation, angiogenesis, and anti-inflammatory responses. Key miRNAs identified include fca-miR-221, fca-let-7f-5p, fca-miR-337-5p, fca-miR-542-5p, fca-miR-24-3p, fca-miR-205, and fca-miR-23a, which promote proliferative, angiogenic, differentiation, and regenerative mechanisms. Additionally, miRNAs with anti-inflammatory effects, such as fca-miR-193a-5p and fca-miR-127-3p, and those positively regulating the immune system, including fca-let-7a-5p and fca-miR-chrC1_18846-5p, were identified. Of particular interest, fca-miR-219-5p (has-miR-6766-3p) has been reported to suppress liver fibrosis.These results underline the therapeutic potential of fADSC-derived exosomes in treating FIC and suggest innovative strategies for feline veterinary medicine.