Zhu GQ et al, 2018: Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile Dysfunction.
Zhu GQ, Jeon SH, Bae WJ, Choi SW, Jeong HC, Kim KS, Kim SJ, Cho HJ, Ha US, Hong SH, Lee JY, Kwon EB, Kim SW.
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Urology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
KEMIMEDI, Seoul, Republic of Korea.
Background: Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED.
Materials and Methods: Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting.
Results: The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1.
Conclusions: Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.
Stem Cells Int. 2018 Aug 29;2018:1302672. doi: 10.1155/2018/1302672. eCollection 2018. FREE ARTICLE
Treatment of patients with erectile dysfunction as a complication to diabetes mellitus (DM) might be difficult because of the vascular damage that is associated with this disease. Numerous clinical studies have shown that improved erectile function can be obtained with Li-ESWT, but the results are inconsistent, sometimes too weak and usually of short duration given the demanding procedure.
The authors of this article present data from extensive experimental in vitro and in vivo studies, the latter carried out in DM-rats. Although some of the theoretical details of theses studies partly are beyond the reviewer’s horizon, the essential message of the report is highly interesting and promising for the future.
The major findings were that when Li-ESWT was combined with mesenchymal stem cell therapy (MCST) the effects on vascular endothelial growth factor, vasodilatation and angiogenesis were significantly better than when ESWT and MCST were used isolated.
According to the authors opinion this extensive basic research provides a sufficient basis for clinical studies and I am willing to agree with the authors that the ideas and treatment principles presented in this experimental report might open a new direction of research in how to treat patients with erectile dysfunction.