Nanotechnology-assisted adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury: In vivo cell tracking, optimized injection dosage, and functional evaluation / 亚洲男科学杂志(英文版)

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.

Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1x10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.