RESEARCH HIGHLIGHTS Nature Reviews Urology 11, 485 (2014); published online 29 July 2014; doi:10.1038/nrurol.2014.185
SEXUAL DYSFUNCTION
Microtissue injection enhances erectile function Microtissues (MTs) created from adiposederived stem cells (ADSCs) could go some way to overcoming issues associated with the single-cell injection strategy in erectile dysfunction (ED) therapy, a preclinical study has shown. Xu and colleagues have demonstrated that intracavernous (IC) injection with MTs results in better retention of cells within the penis, and enhanced restoration of erectile function when compared with intracavernous single-cell injection of ADSCs, in rats that have undergone cavernous nerve (CN) injury to induce ED. MTs were generated using the hanging drop method, and retained the stem cell marker CD105 (endoglin). They expressed collagen IV and NGF (nerve growth factor) in culture. NGF has an important role in promoting peripheral neuronal cell growth, and was not detected in ADSCs cultured in a monolayer. Moreover, expression of Wnt5a, chemokine receptor type 4, and vascular endothelial growth factor, were all increased in MTs, compared
with ADSCs that had been grown in a monolayer, which is suggestive of enhanced developmental capacity. ED was induced by CN crush injury, and treatment (phosphate-buffered saline, single-cell ADSCs cultured in a monolayer or 3-day-old MTs), was administered via IC injection.
‘‘
…MTs results in better retention of cells within the penis, and enhanced restoration of erectile function…
’’
The results revealed that MTs have better retention within the corpus cavernosum than single-cell ADSCs over the 28 days of the study period. Both MTs and ADSCs were detectable in the perisinusoidal connective tissue, and had not differentiated, suggesting the therapeutic mechanism might be paracrine. Neuronal nitric oxide synthase (nNOS) expression was significantly decreased in
NATURE REVIEWS | UROLOGY
penile nerves on CN injury, and both singlecell ADSCs and MTs injection significantly (P ≤0.05) restored nNOS expression, with more nNOS-positive nerves observed in the dorsal arteries after MTs treatment. MTs therapy also prevented the reduction in α-smooth muscle actin expression observed in other treatment groups. Erectile function was partially but significantly (P ≤0.05) recovered in both single-cell ADSCs and MTs treatment, and MTs also produced greater and significant (P ≤0.05) improvement in erectile function over single-cell ADSCs therapy. This preclinical study has shown promising results for the use of MTs in the treatment of ED, with enhanced therapeutic effects over more conventional stem cell injection therapy in a rat model. Louise Stone Original article Xu, Y. et al. Therapeutic potential of adipose-derived stem cell-based micro-tissues in a rat model of postprostatectomy erectile dysfunction. J. Sex. Med. doi:10.1111/jsm.12636
VOLUME 11 | SEPTEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved
SEXUAL DYSFUNCTION
Microtissue injection enhances erectile function Microtissues (MTs) created from adiposederived stem cells (ADSCs) could go some way to overcoming issues associated with the single-cell injection strategy in erectile dysfunction (ED) therapy, a preclinical study has shown. Xu and colleagues have demonstrated that intracavernous (IC) injection with MTs results in better retention of cells within the penis, and enhanced restoration of erectile function when compared with intracavernous single-cell injection of ADSCs, in rats that have undergone cavernous nerve (CN) injury to induce ED. MTs were generated using the hanging drop method, and retained the stem cell marker CD105 (endoglin). They expressed collagen IV and NGF (nerve growth factor) in culture. NGF has an important role in promoting peripheral neuronal cell growth, and was not detected in ADSCs cultured in a monolayer. Moreover, expression of Wnt5a, chemokine receptor type 4, and vascular endothelial growth factor, were all increased in MTs, compared
with ADSCs that had been grown in a monolayer, which is suggestive of enhanced developmental capacity. ED was induced by CN crush injury, and treatment (phosphate-buffered saline, single-cell ADSCs cultured in a monolayer or 3-day-old MTs), was administered via IC injection.
‘‘
…MTs results in better retention of cells within the penis, and enhanced restoration of erectile function…
’’
The results revealed that MTs have better retention within the corpus cavernosum than single-cell ADSCs over the 28 days of the study period. Both MTs and ADSCs were detectable in the perisinusoidal connective tissue, and had not differentiated, suggesting the therapeutic mechanism might be paracrine. Neuronal nitric oxide synthase (nNOS) expression was significantly decreased in
NATURE REVIEWS | UROLOGY
penile nerves on CN injury, and both singlecell ADSCs and MTs injection significantly (P ≤0.05) restored nNOS expression, with more nNOS-positive nerves observed in the dorsal arteries after MTs treatment. MTs therapy also prevented the reduction in α-smooth muscle actin expression observed in other treatment groups. Erectile function was partially but significantly (P ≤0.05) recovered in both single-cell ADSCs and MTs treatment, and MTs also produced greater and significant (P ≤0.05) improvement in erectile function over single-cell ADSCs therapy. This preclinical study has shown promising results for the use of MTs in the treatment of ED, with enhanced therapeutic effects over more conventional stem cell injection therapy in a rat model. Louise Stone Original article Xu, Y. et al. Therapeutic potential of adipose-derived stem cell-based micro-tissues in a rat model of postprostatectomy erectile dysfunction. J. Sex. Med. doi:10.1111/jsm.12636
VOLUME 11 | SEPTEMBER 2014 © 2014 Macmillan Publishers Limited. All rights reserved
