Abstract
Abstract Background and Aims Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising regenerative therapy. However, their clinical application is hampered by the presence of xenogeneic components in the medium. In the present study, we aimed to decipher the regenerative properties of MSC-EVs generated under xeno-free conditions to favor the clinical translation of MSC-EVs. Method MSCs were isolated from human umbilical cord and expanded in fetal bovine serum (FBS) and clinical-grade human platelet lysate (HPL) respectively. MSC-EVs were isolated by differential centrifugation combined with size exclusion chromatography and characterized through transmission electron microscopy, nanoparticle tracking analysis, and exoview. Subsequently, a multi-omics approach, comprising transcriptomics, proteomics, and metabolomics, was employed to investigate the molecular cargo of the MSC-EVs. Finally, in vitro and in vivo functional assays were performed to assess the regenerative potential of MSC-EVs in acute kidney injury. Results Our study demonstrated that HPL promoted MSC-EVs production without compromising EVs characteristics. Multi-omics sequencing revealed the stability of HPL cultured MSC-EVs (H-EVs) from different umbilical cord donors and global functional alterations for MSC-EVs under different culture conditions. In comparison to FBS cultured MSC-EVs (F-EVs), the regenerative potential of H-EVs was enhanced especially angiogenesis associated with increased cargo expression. The in vitro studies demonstrated that H-EVs induced more tube-like structure formation and migration. Further, it significantly reduced kidney capillary sparsity in mice with renal ischemic-reperfusion model. Conclusion Our data provided a comprehensive understanding about H-EVs and demonstrated their potential as a safe and effective regenerative therapy, especially targeting angiogenesis-related disorders.
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