Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

This study aimed to explore the therapeutic effects of adipose-derived stem cells （ADSCs）-based microtissues （MTs） on erectile dysfunction （ED） in streptozotocin （STZ）-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ （60 mg kg-1）, and 8 weeks later, the determined diabetic rats randomly received intracavernous （IC） injection of phosphate buffer solution （PBS）, ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure （ICP）, histopathological changes in corpus cavernosum （CC）, and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor （VEGF）, nerve growth factor （NGF）, and tumor necrosis factor-stimulated gene-6 （TSG-6）. MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase （nNOS） expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

Recruiting endogenous stem cells： a novel therapeutic approach for erectile dysfunction

Transplanted stem cells （SCs）, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction （ED）. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding： （1） SC niche and SC biological features in vitro; （2） localization and mobilization of endogenous SCs; （3） existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

Study of Clinical Practical Model of Urinary System Injury

Background： In order to improve the clinical treatment level of urinary system injury, it is necessary to build tip an animal model of urinary system wound, which is not only analogous to real clinical practice, but also simple and practical. Methods： We have developed the third generation of firearm fragment wound generator based on the first and the second producer. The best explosive charge of the blank cartridge was selected by gradient powder loading experiments. The firearm fragment injuries were made to the bulbous urethra of 10 New Zealand male rabbits. One week preoperatively and 2, 4 and 8 weeks postoperatively, all the animals underwent urethroscopy and urethrography. At 2, 4 and 8 weeks postoperatively, two animals were randomly selected and killed, and the urethra was cut off for pathological examination. Results： The shooting distance of the third generation of firearm fragment wound generator is 2 cm. The best explosive charge of the blank cartridge is 1 g ofnitrocotton. All rabbits survived the procedures and stayed alive until they were killed, h!juries were limited to bulbous urethra and distal urethra. Round damaged areas, 1-1.5 cm in length, on the ventral wall were observed. Ureteroscopy restdts showed that canal diameter gradually shrank by over 50% in 9 rabbits. The rate of success was 90%. Urethrography result noted that a 11.3 cm stricture was formed at the bulbous urethra. Histology results of injured stricture urethra showed that fibrous connective tissue hyperplasia and hyaline degeneration caused further stricture in the canal. Conclusions： The third generation of firearm fragment wound generator imitates the bullet firing process and is more accurate and repeatable. The corresponding rabbit model of traumatic complex urethral stricture simulates the real complex clinical conditions. This animal model provides a standardized platform for clinical researches on treating traumatic injuries to the urinary system.