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Harnessing the mesenchymal stem cell secretome for regenerative urology

Nature Reviews Urology volume 16, pages 363–375 (2019)Cite this article

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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.

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 secretome, which probably include MSC-derived extracellular vesicles in addition to bioactive cytokines.

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Fig. 1: MSC mechanisms of action.
Fig. 2: The MSC secretome in regenerative urology.
Fig. 3: Characterizing the MSC secretome.

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Authors and Affiliations

  1. Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

    Daniel Z. Sun, Benjamin Abelson, Paurush Babbar & Margot S. Damaser

  2. Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA

    Daniel Z. Sun, Benjamin Abelson, Paurush Babbar & Margot S. Damaser

  3. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Daniel Z. Sun, Benjamin Abelson, Paurush Babbar & Margot S. Damaser

  4. Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA

    Margot S. Damaser

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Contributions

D.Z.S. researched data for the article. D.Z.S. and M.S.D. made substantial contributions to discussion of the article contents. D.Z.S., B.A. and P.B. wrote the manuscript. D.Z.S. and M.S.D. reviewed and/or edited the manuscript before submission.

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Correspondence to Daniel Z. Sun.

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M.S.D. declares an option to license her patent on the mesenchymal stem cell secretome in genitourinary disorders. The other authors declare no competing interests.

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Glossary

Transdifferentiation

The conversion of a cell of one tissue lineage into a cell of a different lineage.

Engraftment

The process by which stem cells integrate into host tissue.

Maldifferentiation

The formation of unwanted ectopic tissue (for example, tumour cells).

MSC-conditioned culture medium

(MSC-CCM). Culture medium containing biologically active components that are secreted by mesenchymal stem cells (MSCs).

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Sun, D.Z., Abelson, B., Babbar, P. et al. Harnessing the mesenchymal stem cell secretome for regenerative urology. Nat Rev Urol 16, 363–375 (2019). https://doi.org/10.1038/s41585-019-0169-3

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