Mesenchymal Stem Cells Aid Prostate Surgery Recovery

Review of “Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms” from Stem Cells by Stuart P. Atkinson

One of the most successful anti-cancer strategies still remains the surgical removal of affected tissue. However, invasive surgery can, and does, have unfortunate side effects. This is the case for radical prostatectomy (RP) for aggressive prostate cancer which can leave patients with functional urological disorders [1, 2] such as combined urinary incontinence and erectile dysfunction. 

René Yiou and Anne-Marie Rodriguez sought to assess whether the application of human mesenchymal stem cells (hMSCs) derived from adipose tissue could help to repair tissue damage caused by RP in a rat model [3] with the hope of using this strategy to treat human patients in the future. Their new study in Stem Cells demonstrates that this strategy is both safe and effective and functions through a potent paracrine mechanism [4]. 

To model RP in the rat, the authors used an electrically heated needle to provoke damage and durable impairments in both urinary and erectile functions [3]. When compared to control, hMSC-treated mice demonstrated great improvement in these functions at 15 and 30 days after injection and this continued with time. This correlated with an improvement in muscle cell number and structure (See attached figure showing muscle staining in the striated urethral sphincter (SUS) and in the penis), improved nerve regeneration, and stimulated angiogenesis.

However, tracking of hMSCs demonstrated very low levels of muscle transdifferentiation or engraftment, suggesting that hMSCs promoted repair/regeneration and/or reduced inflammation via paracrine mechanisms. Indeed, the study found that hMSCs secreted various factors associated with tissue repair in a tissue-specific manner and hMSCs found close to penis tissues with neuronal damage expressed different factors when compared to those located in other penis tissues. Lastly, and perhaps most interestingly, the longer-term effects of hMSCs seemed to be due to modification of the host secretion patterns, suggesting a synergistic effect between factors released by hMSCs and host cells in repair/regeneration.

This exciting study shows for the first time that hMSCs can be used to simultaneously treat urinary incontinence and erectile dysfunction through the release of soluble factors and the activation of mediator secretion by the hosts own cells. Additionally, hMSC-injection did not require immune suppression and the authors note that therapeutic effects persisted 3 months after the injury, even after rapid hMSC elimination from the injection site. Hopefully, this paper will lay the foundations for the treatment of human prostatectomy patients in the near future.

References

1. Glickman L, Godoy G, and Lepor H Changes in continence and erectile function between 2 and 4 years after radical prostatectomy. J Urol 2009;181:731-735.
2. Coelho RF, Rocco B, Patel MB, et al. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a critical review of outcomes reported by high-volume centers. J Endourol 2010;24:2003-2015.
3. Khodari M, Souktani R, Le Coz O, et al. Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage. J Sex Med 2012;9:2827-2837.
4. Yiou R, Mahrouf-Yorgov M, Trébeau C, et al. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms. STEM CELLS 2016;34:392-404.