Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats (original) (raw)
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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.
Andrologia, 2010
Stem cell-based therapy targeted at the penile tissue has been lately considered in preclinical studies. This work aimed to assess the effect of intracavernous administration of mesenchymal stem cells (MSCs) in aged rats (n = 100). They were subjected to single intracavernous injection (ICI) of 1.0 million MSCs, followed up for 3, 4 weeks, 3 and 4 months (each group 25 rats) and compared with both adult and aged controls (n = 50). In dissected cavernous tissues, cGMP and histopathology were assessed in addition to intracavernous pressure (ICP) measurement in some anaesthetised rats. The results showed that cavernous tissue cGMP was significantly increased in MSCs transplanted rats in all investigated groups compared with the controls. The mean cavernous cGMP levels after 3 and 4 months of MSCs transplantation were significantly increased compared with those after 3 or 4 weeks. Cavernous tissue ICP measurement showed significant increase in MSCs transplanted groups compared with the controls, more in the long-term follow up than in the shorter one. Histopathological examination detected markedly dilated sinusoidal vascular spaces in the long-term follow-up study. It is concluded that stem cell-based therapy is feasible for age-associated erectile dysfunction and could improve erectile signaling.
Open Access Macedonian Journal of Medical Sciences, 2021
This study investigated the therapeutic role of mesenchymal stem cells (MSCs) on erectile function in a diabetes mellitus erectile dysfunction (DMED) rat model by analyzing the expression of endothelial nitric oxide synthetase (eNOS), vascular endothelial growth factor (VEGF), and the 70 kilodalton heat shock proteins (HSP70). MSCs were isolated from umbilical cords (UCs), and their characteristics identified by flow cytometry and osteogenic differentiation analysis. Thirty 8-week-old rats were divided into four groups: sham, control, T1, and T2. After a 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin (STZ) to induce DM. At 8 weeks after STZ injection, rats with DMED were classified into four groups, sham, control group [DMED rats received 500 μL phosphate buffer saline (PBS)]; T1 [DMED rats treated with 500 μL PBS containing 1 × 106 UC-MSCs]; T2 [DMED rats treated with 500 μL PBS containing 2 × 106 UC-MSCs]. Eight weeks after MSCs admini...
Erectile dysfunction treated with intracavernous stem cells: A promising new therapy?
Revista internacional de andrologia
In the past decades, great interest has been shown in the development of new therapies for erectile dysfunction. Stem cell therapy has generated promising results in numerous preclinical trials in animal models, which is why has led to the development of the first clinical trials in humans. The main cause involved in the pathophysiology of erectile dysfunction is vascular damage related to endothelial and neuronal injury. The interest in stem cell therapy is justified by their capability to differentiate into specific damaged tissues, including endothelium and nervous tissue, and induction of the host own cell proliferation. Despite the great effort of the many studies carried out to date, knowledge about biological effects, therapeutic efficacy and safety of stem cells therapy for erectile dysfunction is still very limited.
Therapeutic angiogenesis as a potential future treatment strategy for erectile dysfunction
The world journal of men's health, 2012
The cavernous endothelium plays a crucial role in regulating the tone of the underlying smooth muscle and physiologic penile erection. Recently, the link between erectile dysfunction (ED) and cardiovascular disease was unveiled, and the main etiology of ED was found to be vasculogenic. Although oral phosphodiesterase-5 inhibitors are generally effective for men with ED, such therapies do not cure underlying vasculopathy in the corpus cavernosum tissue. This review addresses current preclinical protein, gene, and cell or stem cell therapies for enhancing cavernous endothelial regeneration and restoring erectile function.
The Endothelial–Erectile Dysfunction Connection: An Essential Update
The Journal of Sexual Medicine, 2009
Introduction. The endothelial monolayer plays a crucial role in the vasodilation and hemodynamic events involved in erection physiology. Due to its relevant functions, a close link has been established between endothelial integrity and erectile dysfunction (ED). Endothelial dysfunction is induced by the detrimental actions of vascular risk factors (VRFs), identified as common correlates for the development of cardiovascular disease and ED. It is currently recognized that ED is the early harbinger of a more generalized vascular systemic disorder, and, therefore, an evaluation of endothelial health in ED patients should be of prime relevance. Several noninvasive methods for endothelial function assessment have been proposed, including the Penile Nitric Oxide Release Test (PNORT). Aim. To highlight the most recent gathered knowledge on basic and clinical mechanisms underlying loss of cavernosal endothelial function promoted by VRFs and to discuss local and systemic methods for endothelial function assessment in ED individuals, focusing on the PNORT. Main Outcome Measures. A complete revision on the novel basic and clinical links between endothelial and ED. Methods. A systematic review of the literature regarding the aforementioned issues. Results. Risk factor-associated cavernosal endothelial dysfunction is mostly induced by unifying mechanisms, including oxidative stress and impaired endothelial nitric oxide functional activities, which present clinically as ED. Several techniques to evaluate endothelial dysfunction were revised, with advantages and limitations debated, focusing on our detailed expertise using the PNORT method. Conclusions. The established endothelial-erectile dysfunction connection was thoroughly revised, from basic mechanisms to the clinical importance of endothelial dysfunction assessment as diagnosis for generalized vascular disease. Further studies are required to disclose efficient approaches to repair disabled endothelium and both restore and prevent endothelial dysfunction. Costa C, and Virag R. The endothelial-erectile dysfunction connection: