Harnessing the mesenchymal stem cell secretome for regenerative urology

• Published in: Nature reviews. Urology 2019-06, Vol.16 (6), p.363-375
• Main Authors: Sun, Daniel Z., Abelson, Benjamin, Babbar, Paurush, Damaser, Margot S.
• Format: Article
• Language: English
• Subjects: 631/532/2074; 692/308/2171; 692/4025/2768; Care and treatment; Cytokines; Development and progression; Erectile dysfunction; Extracellular Vesicles; Humans; Kidney diseases; Medicine; Medicine & Public Health; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Methods; Regenerative medicine; Regenerative Medicine - methods; Review Article; Secretory Pathway; Stem cells; Transplantation; Urologic diseases; Urologic Surgical Procedures - methods; Urology; Urology - methods
• ISSN: 1759-4812; 1759-4820
• DOI: 10.1038/s41585-019-0169-3

The extensive arsenal of bioactive molecules secreted by mesenchymal stem cells (MSCs), known as the secretome, has demonstrated considerable therapeutic benefit in regenerative medicine. Investigation into the therapeutic potential of the secretome has enabled researchers to replicate the anti-inflammatory, pro-angiogenic and trophic effects of stem cells without the need for the cells themselves. Furthermore, treatment with the MSC secretome could circumvent hurdles associated with cellular therapy, including oncogenic transformation, immunoreactivity and cost. Thus, a clear rationale exists for investigating the therapeutic potential of the MSC secretome in regenerative urology. Indeed, preclinical studies have demonstrated the therapeutic benefits of the MSC secretome in models of stress urinary incontinence, renal disease, bladder dysfunction and erectile dysfunction. However, the specific mechanisms underpinning therapeutic activity are unclear and require further research before clinical translation. Improvements in current proteomic methods used to characterize the secretome will be necessary to provide further insight into stem cells and their secretome in regenerative urology. The mesenchymal stem cell (MSC) secretome offers numerous advantages over cell-based therapy, with similar therapeutic effects. Here, the authors discuss the preclinical therapeutic promise of the MSC secretome in regenerative urology, highlighting putative mechanisms of action, characterization methods and future perspectives. Key points Stem cells possess anti-inflammatory, pro-angiogenic and anti-apoptotic properties that might have therapeutic benefit in urological diseases for which conventional therapies are lacking. The acellular secretome of mesenchymal stem cells (MSCs) exerts similar therapeutic benefits to that of traditional cell-based therapy. The MSC secretome avoids problems associated with traditional stem cell therapy, including oncogenic transformation, immunoreactivity and cost. The MSC secretome exerts therapeutic benefits in preclinical models of stress urinary incontinence, acute and chronic renal disease, bladder dysfunction and erectile dysfunction. The specific mechanisms through which the MSC secretome exerts its therapeutic effects require further investigation, but they probably involve multiple MSC-derived bioactive cytokines that function synergistically. Proteomic strategies have been used to characterize the active components of the MSC secre