Gene and stem cell therapy for erectile dysfunction (original) (raw)
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Emerging gene and stem cell therapies for the treatment of erectile dysfunction
Nature Reviews Urology, 2010
| Erectile dysfunction is a prevalent condition that leads to significant morbidity and distress, not just for affected men but also for their partners. Very few currently available treatments ameliorate the underlying causes of the disorder and 'cure' the disease state. Much recent effort has been focused on the development of gene and cell-based approaches to rectify the molecular and tissue defects responsible for ED. Gene therapy has been investigated in animal models as a means to restore normal function to the penis; at this time, however, only one human trial has been published in the peer-reviewed literature. Recent gene therapy studies have focused on the modulation of enzymes associated with the NOS/cGMP pathway, and supplementation of trophic factors, peptides and potassium channels. Stem cell therapy has been a topic of interest in more recent years but there are currently very few published reports in animal models and none in human men. Although stem cell therapy offers the potential for restoration of functional tissues, legitimate concerns remain regarding the long-term fate of stem cells. The long-term safety of both gene and stem cell therapy must be thoroughly investigated before large-scale human studies can be considered.
Stem cell treatment of erectile dysfunction
Advanced Drug Delivery Reviews, 2014
a b s t r a c t a r t i c l e i n f o Erectile Dysfunction (ED) is a common disease that typically affects older men. While oral type-5 phosphodieserase inhibitors (PDE5Is) represent a successful first-line therapy, many patients do not respond to this treatment leading researchers to look for alternative treatment modalities. Stem cell (SC) therapy is a promising new frontier for the treatment of those patients and many studies demonstrated its therapeutic effects. In this article, using a Medline database search of all relevant articles, we present a summary of the scientific principles behind SCs and their use for treatment of ED. We discuss specifically the different types of SCs used in ED, the methods of delivery tested, and the methods attempted to enhance SC therapy effect. In addition, we review the current preclinical literature on SC therapy for ED and present a summary of its findings in addition to the single clinical trial published. j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / a d d r Please cite this article as: A. Alwaal, et al., Stem cell treatment of erectile dysfunction, Adv. Drug Deliv. Rev. (2014), http://dx.
American Journal of Physiology-heart and Circulatory Physiology, 2006
Mesenchymal stem cells (MSCs) can be used in adult stem cell-based gene therapy for vascular diseases. To test the hypothesis that MSC alone or eNOS modified MSCs can be used for treatment of erectile dysfunction (ED), syngeneic rat MSCs (rMSCs) were isolated, ex vivo expanded, transduced with adenovirus containing endothelial nitric oxide synthase (eNOS), and injected into the penis of aged rats. Histological analysis demonstrated that rMSCs survived for at least 21 days in corporal tissue after intracavernous injection and an inflammatory response was not induced. Intracavernous administration of eNOS-modified rMSCs improved the erectile response in aged rats at 7 and 21 days after injection. The increase in erectile function was associated with increased eNOS protein, NOS activity and cGMP levels. rMSCs alone increased erectile function of aged rats at day 21, but not at day 7, with the transplanted cells exhibiting positive immunostaining for several endothelial and smooth muscle cell markers.
Gene therapy and erectile dysfunction: the current status
Asian Journal of Andrology, 2007
Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED. (Asian J Androl 2007 Jan; 9: 8-15 )
Emerging tools for erectile dysfunction: a role for regenerative medicine
Nature Reviews Urology, 2012
| Erectile dysfunction (ED) is the most common sexual disorder reported by men to their healthcare 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.
Frontiers in gene therapy for erectile dysfunction
International Journal of Impotence Research, 2003
Complete sequencing of the human genome has made possible a new age of molecular medicine. The utilization of sophisticated genomic technologies has important implications to the understanding, diagnosis and treatment of erectile dysfunction. This report will review one aspect of the impact of the genomic revolution on urology, to wit, the preclinical evidence emerging from several laboratories indicating that gene therapy for erectile dysfunction may well provide the first safe and effective application of gene therapy to the treatment of human smooth muscle disease. The molecular targets explored thus far have concentrated largely on manipulating various aspects of the nitric oxide/guanylate cyclase/cGMP system, although genetic modulation of growth factors, calcium sensitization mechanisms and potassium channel expression have also been explored. Cellbased gene therapy techniques are also being explored. The apparent preclinical success of virtually all of these gene-based strategies reflects the multifactorial nature of erectile disease as well as the numerous regulatory mechanisms available for restoring erectile capacity. While technical hurdles remain with respect to the choice of delivery vectors, molecular target validation and duration of efficacy, 'proof-of-concept' has clearly been documented. The ultimate goal of gene therapy is to provide a safe, effective and specific means for altering intracavernous pressure 'on demand', while simultaneously eliminating the necessity for other forms of therapy, and moreover, without altering resting penile function, or the physiology of other organ systems. It is in these arenas that the groundbreaking potential of gene transfer technology to the treatment of erectile dysfunction will be fully tested. In fact, the potential benefits of the application of gene transfer techniques to this important medical problem is just now beginning to be appreciated/recognized.
Application of Stem Cell in Human Erectile Dysfunction – A Systematic Review
Research and Reports in Urology
Erectile dysfunction is a health problem that arises from various conditions and causes an impaired quality of life with a significant health burden. Regenerative and stem cell therapies are some of the potential treatments for erectile dysfunction. This study aimed to review the available information in the literature regarding the use of stem cells in the treatment of erectile dysfunction. Methods: This study is a systematic review conducted based on the PubMed, Google Scholar, Cochrane, and DOAJ databases. Literature searching was conducted in English and included articles from 2000 to 2020. Results: The result was a total of 318 articles. Following the elimination process, 9 articles remained in the final analysis. The analyzed studies included 164 patients with erectile dysfunction with various medical conditions. Several stem cell types have been used for treating erectile dysfunction, including mesenchymal stem cell, placental matrix-derived stem cell, mesenchymal stem cellderived exosome, adipose-derived stem cell, bone marrow-derived mononuclear stem cell, and umbilical cord blood stem cell. Generally, stem cell therapy showed a good efficacy and safety profile, although not enough studies on the protocol, dosage, and mechanism of action. Conclusion: Stem cell therapy has a good therapeutic potential in erectile dysfunction, the available data from the literature could be the base of usage of stem cells in the treatment of erectile dysfunction although need more research for broader usage.
Biology of Reproduction, 1997
Erectile dysfunction is mainly due to the inability of the cavernosal smooth muscle of the penis to undergo complete relaxation. In the aging rat model, erectile dysfunction is accompanied by a reduction of penile smooth muscle compliance and, in very old animals, by a decrease in penile nitric oxide synthase (NOS), which is responsible for the synthesis of the mediator of penile erection, nitric oxide (NO). We have investigated whether the stimulation of penile NOS expression by local induction or gene therapy can mitigate erectile dysfunction in the aged rat. A mix of iNOS (inducible NOS) inducers was continuously delivered to the penises of 5-("adult"), 20-("old"), and 30-("very old") mo-old rats for 3-6 days, and the erectile response to electrical field stimulation of the cavernosal nerve was measured. The erectile dysfunction observed in old and very old rats as compared to adult animals was ameliorated by treatment with iNOS inducers. Penile iNOS was detectable in the penis of these rats by Western blot, NADPH diaphorase, and NOS activity assays. Inducible NOS was inducible in vitro in both rat and human corpora cavernosal tissue and in rat penile smooth muscle cells (RPSMC), as shown by Western blots. However, NO synthesis in cavernosal tissue upon iNOS protein induction remained low, indicating that the increased NOS levels were under physiological control. The iNOS cDNA was cloned from induced RPSMC mRNA and generated by reverse transcriptase polymerase chain reaction (RT-PCR) from induced human penile smooth muscle cells and corporal tissue. The coding regions from both the rat (RPiNOS) and human (HPiNOS) penile iNOS showed several amino acid differences from their analogous isoform in nonpenile tissues. RPiNOS cDNA injected into the penis mitigated the aging-associated erectile dysfunction. The iNOS construct was detected in cavernosal tissue by PCR, and its expression by RT-PCR and Western blots. These results open the way for the possible use of NOS isoforms in the management of erectile dysfunction.