Harnessing the mesenchymal stem cell secretome for regenerative urology

Abstract

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.

Figure 1. Putative mechanisms of action of MSCs. MSCs either differentiate or secrete soluble factors, some of which are contained in extracellular vesicles. They exert trophic, angiogenic, immunosupressive, anti-fibrotic, and anti-apoptotic effects which promote regeneration of injured tissue.

Figure 2.

A summary of the effects of the MSC secretome on urological pathology as demonstrated in pre-clinical studies