Corrigendum to “Both Immediate and Delayed Intracavernous Injection of Autologous Adipose-derived Stromal Vascular Fraction Enhances Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury” [Eur Urol 2012;62:720–7]

Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA 94143-0738, USA.
European Urology (Impact Factor: 13.94). 02/2012; 62(4):720-7. DOI: 10.1016/j.eururo.2012.02.003
Source: PubMed


Intracavernous injection of cultured adipose-derived stem cells (ADSCs) effectively restores erectile function in cavernous nerve (CN)-injured rats when administered at the time of injury. However, culturing exposes ADSCs to the risk of contamination and dedifferentiation.
Explore the effect of uncultured autologous adipose-derived stromal vascular fraction (SVF) on improving erectile function in a rat model of CN injury when administered at the time of injury or 4 wk after injury.
Eighty-nine male Sprague Dawley rats were randomly divided into four groups. CN injury or sham surgery was performed at the start of the study, and rats were treated with either SVF or vehicle. Functional testing and histologic analysis were performed 12 wk after CN crush or sham surgery.
We used intracavernous injection of saline immediately after CN crush (n=23), intracavernous injection of SVF immediately after CN crush (n=17), intracavernous injection of SVF 4 wk after CN crush (n=23), or sham surgery (n=26). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied intracavernous pressure (ICP) response to CN electrostimulation and performed histologic examination of midpenile cross-sections. Data were analyzed using one-way analysis of variance followed by the Tukey-Kramer test.
Both immediate and delayed treatment with SVF resulted in a significantly increased ICP-to-mean arterial pressure ratio compared with the vehicle-treated group. Both immediate and delayed treatment with SVF significantly increased expression of neuronal nitric oxide synthase and neurofilament in dorsal penile nerves compared to the vehicle group. Furthermore, the smooth muscle-to-collagen ratio within the corpus cavernosum was significantly improved in both of the SVF groups compared to vehicle-treated rats. The main limitation of the study is the lack of determination of the SVF components.
Uncultured autologous SVF injected immediately or 4 wk after CN crush improved erectile function, promoted nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN injury.

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Available from: Haiyang Zhang, Jan 07, 2014
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    • "Injected cells recruited to the MPG in injured rats, not in sham, soon after injury, but not permanently engrafted [35] CNI (crush, rat) MDSC 4 weeks Increased cGMP levels in penile tissue [36] CNI (crush, rat) ADSC 2 or 7 days Both autologous and allogeneic ADSCs exit the CC within days of injection and CNI; migrates preferentially towards bone marrow [37] Diabetes type I (rat) BMSC 4 weeks Increased smooth muscle and endothelial markers. Enhanced penile VEGF expression [18] CNI (crush, rat) SVF 3 months Improved nNOS and neurofilament staining in the dorsal penile nerve. Improved smooth muscle/collagen ratio in erectile tissue [38] Pelvic irradiation ADSC 6 weeks Improved nNOS expression in dorsal penile nerve and MPG, improved smooth muscle content, EdU (cell marker)-positive cells migrated into the MPG [39] CNI (crush, rat) BMSC 4 weeks Improved nNOS and eNOS levels [22] Diabetes type I (rat) BMSC or BMSC-conditioned culture medium 4 weeks In-vitro: secretion of neurotrophic molecules by BMSC. "
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    ABSTRACT: Introduction Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause. Recently, therapies based on stem cells (SCs) have had an increasing attention for their potential to restore erectile function. Preclinical studies showed that these cells might reverse the pathophysiological changes leading to ED, rather than treating the symptoms of ED. This review is intended to provide an overview of contemporary reports on the use of SCs to treat ED. Methods We made an extensive search for reports on SC-based therapy for the management of ED, published in English between 1966 and 2013, using the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar and Pubmed, with the search terms ‘erectile dysfunction’, ‘stem cells’, ‘multipotent stromal cells’, ‘adipose (tissue) derived stem cells’, ‘bone-marrow derived stem cells’, ‘animal model’, ‘diabetes’, ‘ageing’, ‘Peyronie’s Disease’ and ‘cavernous nerve injury’. Results Fifty-four papers were identified and contributed, either as an original research report or review thereof, to this review. Several preclinical studies addressed SC-based therapies for the recovery of erectile function caused by a variety of both chronic and acute conditions. Overall, these studies showed beneficial effects of SC therapy, while evidence on the mechanisms of action of SC therapy varied between studies. One clinical trial investigated the short-term effects of SC therapy in diabetic patients with ED. Two more clinical trials are currently recruiting patients. Conclusions The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED.
    Full-text · Article · Sep 2013 · Arab Journal of Urology
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    • "Their results showed that CN injury upregulates SDF-1 expression in the MPG and thereby attracts intracavernously injected ADSCs. Qiu et al. (2012) found that uncultured autologous adipose-derived stem vascular fraction (SVF) injected immediately or 4 weeks after CN crush improved erectile function, promoted nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN injury. Nitric oxide (NO) is known as the most important neurotransmitter that mediates the relaxation of SM layer present in the corpus cavernosum and it is the main mediator of penile erection (Becker et al. 2002; Burnett and Musicki 2005). "
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    ABSTRACT: The aim of this study was to investigate effects of intracavernous injection of adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Thirty Sprague-Dawley male rats were randomly divided into three equal groups: one group underwent sham operation, while two groups underwent bilateral CN crush. Crush-injury group was treated at the time of injury with intracavernous injection of ADSCs, or injured control group with no further intervention. Erectile function was assessed by CN electrostimulation after 3 months. Penile tissue and crushed nerves were collected for histology. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate intracavernous injection of ADSCs, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the intracavernous injection of ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibers than the injured control group but fewer than the sham group. Intracavernous injection of ADSCs treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. These results show that the intracavernous injection of ADSCs to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that penile injection of ADSCs can improve recovery of erectile function in a rat model of neurogenic ED.
    Preview · Article · Nov 2012 · Cellular and Molecular Neurobiology
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    ABSTRACT: Erectile dysfunction (ED) is the most common sexual disorder reported by men to their health-care providers and the most investigated male sexual dysfunction. Currently, the treatment of ED focuses on 'symptomatic relief' of ED and, therefore, tends to provide temporary relief rather than providing a cure or reversing the cause. The identification of a large population of "difficult-to-treat" patients has triggered researchers to identify novel treatment approaches, which focus on cure and restoration of the underlying cause of ED. Regenerative medicine has developed extensively in the past few decades and preclinical trials have emphasized the benefit of growth factor therapy, gene transfer, stem cells and tissue engineering for the restoration of erectile function. Development of clinical trials involving immunomodulation in postprostatectomy ED patients and the use of maxi-K channels for gene therapy are illustrative of the advances in the field. However, the search for novel treatment targets and a wealth of preclinical studies represent a dynamic and continuing field of enquiry.
    Full-text · Article · Jul 2012 · Nature Reviews Urology
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