madman
Super Moderator
Abstract
Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.
INTRODUCTION
Erectile dysfunction (ED) is defined as the persistent or recurrent inability to attain or maintain an adequate erection to reach satisfaction in sexual intercourse[1]. Although this condition does not directly coincide with serious health problems, it correlates with the decline in the quality of life[2]. Moreover, ED has been determined to be more common in men with diabetes mellitus (DM). Previous studies have shown that the prevalence of ED in DM is very high, i.e., at 67.4%, among those with DM[3]. Thus, DM can be regarded as a major risk factor for acquiring sexual dysfunction in men, increasing the risk of ED in men with DM three times higher than that in those without diabetes[4].
MECHANISM OF DIABETIC ED
Erection is a condition when the penile organ becomes rigid and elevated as a result of the erectile tissue being filled with blood. It is modulated by several mechanisms involving endothelial cells and the autonomic nervous function. To better understand the pathogenesis of ED, we need to comprehend the physiological process of erection, as discussed briefly below.
Three key processes occur during erection: (1) The neurologically mediated arterial inflow; (2) The relaxation of smooth muscle within the corpora spongiosa to allow the blood to fill the penile vasculature; and (3) The obstruction of the veins to retain the blood within the penile vasculature[5].
In response to sexual stimuli, the brain transmits parasympathetic signals through the spinal cord. The signal then reaches the non-adrenergic non-cholinergic neuronal terminals, which will then induce the production of nitric oxide (NO) by neuronal NO synthase (nNOS). Likewise, the endothelium also produces NO via the activation of endothelial NO synthase (eNOS). eNOS and nNOS act as endothelial and neuronal regulators, respectively. Then, the NO will be transported to the corpora spongiosa where it converts GTP to cyclic guanosine monophosphate (cGMP) with the help of the guanylate cyclase enzyme. The cGMP induces smooth muscle relaxation, allowing arterial flow to fill the cavernosal space. cGMP also potentiates protein kinase G activity that leads to free intracellular calcium being taken up by the endoplasmic reticulum, causing a decrease in calcium flux and an increase in potassium flux from the cells and in turn causing depolarization followed by the relaxation of vascular smooth muscle. When the cavernosal space congests with blood, the veins become compressed and occluded which traps the blood in the cavernosal space during tumescence[1,5,6].
*Based on its mechanism, the pathological causes of diabetic-induced ED can be classified into several different categories, i.e., endothelial, neuronal, and endocrinal causes, and others, such as psychological and diabetic-related infections and multiple drug prescriptions. However, all of these dysfunctions can intertwine to form ED (Figure 1).
*Endothelial factors
*Neuronal factors
*Endocrine factors
Hypogonadotropic hypogonadism occurs in approximately 30%-40% of men with type 2 diabetes[21]. This condition reduces the production of testosterone, which. has been identified to stimulate the synthesis, storage, and release of pro-erectogenic neurotransmitters; modulate neuronal activity, receptor sensitivity, neurotransmitter liberation, and socio-sexual behavior (increasing libido); and positively influence the levels of dopamine, NO, oxytocin, etc.[1]. In a population-based cohort, the prevalence of hypogonadism in men with ED was 35% compared with 22.7% in men without ED [22]. A study in Japan conducted by Imai et al[23] showed that decreased testosterone has been associated with severe or moderate ED as opposed to men with mild or no ED and is a risk factor for the development of ED.
*EVALUATION OF ED
*TREATMENT APPROACHES OF DIABETIC ED
-Lifestyle modifications
-Pharmacological approach
-Vacuum and surgical approach
*STEM CELLS AS A FUTURE THERAPY FOR DIABETIC ED
-Classification of stem cells
-Current progress in stem cell therapy for diabetic ED
-Possible mechanisms of stem cell therapy for diabetic ED
CONCLUSION
Overall, based on the published data, it seems that stem cell therapy can become an alternative approach for the treatment of diabetic ED in the future. Stem cells can promote recovery and regeneration of the penile tissue following damage due to inflammation and free radicals. Studies reviewed in this paper, which are almost entirely conducted on experimental animals, certainly require further follow-up research. Information on stem cell research for ED treatment remains to be limited, but it can form the basis to develop further research in this area. In particular, larger human studies with appropriate research designs are needed to provide more objective information on the possibility of translational application.
Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.
INTRODUCTION
Erectile dysfunction (ED) is defined as the persistent or recurrent inability to attain or maintain an adequate erection to reach satisfaction in sexual intercourse[1]. Although this condition does not directly coincide with serious health problems, it correlates with the decline in the quality of life[2]. Moreover, ED has been determined to be more common in men with diabetes mellitus (DM). Previous studies have shown that the prevalence of ED in DM is very high, i.e., at 67.4%, among those with DM[3]. Thus, DM can be regarded as a major risk factor for acquiring sexual dysfunction in men, increasing the risk of ED in men with DM three times higher than that in those without diabetes[4].
MECHANISM OF DIABETIC ED
Erection is a condition when the penile organ becomes rigid and elevated as a result of the erectile tissue being filled with blood. It is modulated by several mechanisms involving endothelial cells and the autonomic nervous function. To better understand the pathogenesis of ED, we need to comprehend the physiological process of erection, as discussed briefly below.
Three key processes occur during erection: (1) The neurologically mediated arterial inflow; (2) The relaxation of smooth muscle within the corpora spongiosa to allow the blood to fill the penile vasculature; and (3) The obstruction of the veins to retain the blood within the penile vasculature[5].
In response to sexual stimuli, the brain transmits parasympathetic signals through the spinal cord. The signal then reaches the non-adrenergic non-cholinergic neuronal terminals, which will then induce the production of nitric oxide (NO) by neuronal NO synthase (nNOS). Likewise, the endothelium also produces NO via the activation of endothelial NO synthase (eNOS). eNOS and nNOS act as endothelial and neuronal regulators, respectively. Then, the NO will be transported to the corpora spongiosa where it converts GTP to cyclic guanosine monophosphate (cGMP) with the help of the guanylate cyclase enzyme. The cGMP induces smooth muscle relaxation, allowing arterial flow to fill the cavernosal space. cGMP also potentiates protein kinase G activity that leads to free intracellular calcium being taken up by the endoplasmic reticulum, causing a decrease in calcium flux and an increase in potassium flux from the cells and in turn causing depolarization followed by the relaxation of vascular smooth muscle. When the cavernosal space congests with blood, the veins become compressed and occluded which traps the blood in the cavernosal space during tumescence[1,5,6].
*Based on its mechanism, the pathological causes of diabetic-induced ED can be classified into several different categories, i.e., endothelial, neuronal, and endocrinal causes, and others, such as psychological and diabetic-related infections and multiple drug prescriptions. However, all of these dysfunctions can intertwine to form ED (Figure 1).
*Endothelial factors
*Neuronal factors
*Endocrine factors
Hypogonadotropic hypogonadism occurs in approximately 30%-40% of men with type 2 diabetes[21]. This condition reduces the production of testosterone, which. has been identified to stimulate the synthesis, storage, and release of pro-erectogenic neurotransmitters; modulate neuronal activity, receptor sensitivity, neurotransmitter liberation, and socio-sexual behavior (increasing libido); and positively influence the levels of dopamine, NO, oxytocin, etc.[1]. In a population-based cohort, the prevalence of hypogonadism in men with ED was 35% compared with 22.7% in men without ED [22]. A study in Japan conducted by Imai et al[23] showed that decreased testosterone has been associated with severe or moderate ED as opposed to men with mild or no ED and is a risk factor for the development of ED.
*EVALUATION OF ED
*TREATMENT APPROACHES OF DIABETIC ED
-Lifestyle modifications
-Pharmacological approach
-Vacuum and surgical approach
*STEM CELLS AS A FUTURE THERAPY FOR DIABETIC ED
-Classification of stem cells
-Current progress in stem cell therapy for diabetic ED
-Possible mechanisms of stem cell therapy for diabetic ED
CONCLUSION
Overall, based on the published data, it seems that stem cell therapy can become an alternative approach for the treatment of diabetic ED in the future. Stem cells can promote recovery and regeneration of the penile tissue following damage due to inflammation and free radicals. Studies reviewed in this paper, which are almost entirely conducted on experimental animals, certainly require further follow-up research. Information on stem cell research for ED treatment remains to be limited, but it can form the basis to develop further research in this area. In particular, larger human studies with appropriate research designs are needed to provide more objective information on the possibility of translational application.
