madman
Super Moderator
Revisiting the Regenerative Therapeutic Advances Towards Erectile Dysfunction
Abstract: Erectile dysfunction (ED) is an inability to attain or maintain adequate penile erection for successful vaginal intercourse, leading to sexual and relationship dissatisfaction. To combat ED, various surgical and non-surgical approaches have been developed in the past to restore erectile functions. These therapeutic interventions exhibit significant impact in providing relief to patients; however, due to their associated adverse effects and lack of long-term efficacy, newer modalities such as regenerative therapeutics have gained attention due to their safe and prolonged efficacy. Stem cells and platelet-derived biomaterials contained in platelet-rich plasma (PRP) are thriving as some of the major therapeutic regenerative agents. In recent years, various preclinical and clinical studies have evaluated the individual, as well as combined of stem cells and PRP to restore erectile function. Being rich in growth factors, chemokines, and angiogenic factors, both stem cells and PRP play a crucial role in regenerating nerve cells, myelination of axons, homing and migration of progenitor cells, and anti-fibrosis and anti-apoptosis of damaged cavernous nerve in corporal tissues. Further, platelet-derived biomaterials have been proven to be a biological supplement for enhancing the proliferative and differentiation potential of stem cells towards neurogenic fate. Therefore, this article comprehensively analyzes the progresses of these regenerative therapies for ED.
1. Introduction
Erectile dysfunction (ED) severely impacts the personal, social, and sexual life of patients [1,2] and is found be more frequent among the middle aged and aging population [3]. In the context of sexual health, ED affects all domains such as desire, arousal, erectile function, and ejaculation/orgasm [4]. Therefore, its early diagnosis and management are highly imperative. The etiology of ED may include aging, psychological disorders, spinal injury/nervous disorders, diabetes, sleep apnea, chronic obstructive pulmonary disease, renal insufficiency, cavernous fibrosis, Peyronie’s disease, and the adverse effect of drugs (Figure 1) [3]. In addition, excessive use of drugs and over stress also lead to progressive ED. The progression of diabetes, cardiovascular disorders, and hypertension also pose a high risk of ED and hence decreased libido.
Figure 1. Pathophysiology of erectile dysfunction (ED). Aging, psychogenic issues, drugs, nerve injury, and diabetes represent major etiological factors leading to physiological changes such as excess collagen deposition, endothelial dysfunction, cavernous fibrosis, arterial insufficiency in penile corpus cavernosum, and loss of erectile function.
6. Discussion and Future Prospects
The current treatment options to overcome ED have enormously improved the sexual life of males and therefore play a crucial role in restoring confidence and relationships. However, these treatments could only provide limited recovery from CNI-induced ED. The demand for highly efficacious and long-lasting therapeutic options has prompted the scientific community to explore the potential of regenerative medicine. The current surge in scientific, preclinical, and clinical studies in regenerative therapies including stem cells and PRP has not only increased the therapeutic expectations, but also uncovered the scientific rationale behind them. Both the stem cell, as well as PRP-based therapies have imparted nerve cell regeneration through secretion of growth and nerve factors and anti-apoptotic activities. The pre-clinical studies have shown significant improvement in terms of restoring erectile functions through cell-based therapies in ED animal models, which could be improved through LI-ESWT by increasing cell viability, proliferation, and multilineage differentiation [144]. A recent study showed an improved therapeutic efficacy of Schwann cells with overexpressing GDNF in CNI-induced ED rats [145]. Thus, the overexpression of relevant growth factors may be targeted to promote rapid stem cell-mediated regeneration of damaged cavernosal nerves. Moreover, the stem cells in combination with non-surgical and pharmacological agents might prove to be a crucial therapeutic strategy for ED.
Similar to stem cells, PRP has also been widely studied for its regenerative potential, which is ascribed to its capability to secrete growth factors, cytokines, and ECM, thereby promoting migration, proliferation, stabilization, and differentiation of endothelial, fibroblast, and stem cells [146]. Therefore, the concentrations of platelet, cytokine, and growth factors need to be well established to achieve the optimal therapeutic impact of PRP [147]. Further, regenerative potential could be enhanced through combining both stem cells and PRP. However, to date, the studies on PRP and stem cells remain limited to establishing the clinical efficacy and safety for CNI-induced ED. Hence, extensive, multicenter, and large preclinical and clinical studies are required for the acceptance of these regenerative therapeutics.
Abstract: Erectile dysfunction (ED) is an inability to attain or maintain adequate penile erection for successful vaginal intercourse, leading to sexual and relationship dissatisfaction. To combat ED, various surgical and non-surgical approaches have been developed in the past to restore erectile functions. These therapeutic interventions exhibit significant impact in providing relief to patients; however, due to their associated adverse effects and lack of long-term efficacy, newer modalities such as regenerative therapeutics have gained attention due to their safe and prolonged efficacy. Stem cells and platelet-derived biomaterials contained in platelet-rich plasma (PRP) are thriving as some of the major therapeutic regenerative agents. In recent years, various preclinical and clinical studies have evaluated the individual, as well as combined of stem cells and PRP to restore erectile function. Being rich in growth factors, chemokines, and angiogenic factors, both stem cells and PRP play a crucial role in regenerating nerve cells, myelination of axons, homing and migration of progenitor cells, and anti-fibrosis and anti-apoptosis of damaged cavernous nerve in corporal tissues. Further, platelet-derived biomaterials have been proven to be a biological supplement for enhancing the proliferative and differentiation potential of stem cells towards neurogenic fate. Therefore, this article comprehensively analyzes the progresses of these regenerative therapies for ED.
1. Introduction
Erectile dysfunction (ED) severely impacts the personal, social, and sexual life of patients [1,2] and is found be more frequent among the middle aged and aging population [3]. In the context of sexual health, ED affects all domains such as desire, arousal, erectile function, and ejaculation/orgasm [4]. Therefore, its early diagnosis and management are highly imperative. The etiology of ED may include aging, psychological disorders, spinal injury/nervous disorders, diabetes, sleep apnea, chronic obstructive pulmonary disease, renal insufficiency, cavernous fibrosis, Peyronie’s disease, and the adverse effect of drugs (Figure 1) [3]. In addition, excessive use of drugs and over stress also lead to progressive ED. The progression of diabetes, cardiovascular disorders, and hypertension also pose a high risk of ED and hence decreased libido.
Figure 1. Pathophysiology of erectile dysfunction (ED). Aging, psychogenic issues, drugs, nerve injury, and diabetes represent major etiological factors leading to physiological changes such as excess collagen deposition, endothelial dysfunction, cavernous fibrosis, arterial insufficiency in penile corpus cavernosum, and loss of erectile function.
6. Discussion and Future Prospects
The current treatment options to overcome ED have enormously improved the sexual life of males and therefore play a crucial role in restoring confidence and relationships. However, these treatments could only provide limited recovery from CNI-induced ED. The demand for highly efficacious and long-lasting therapeutic options has prompted the scientific community to explore the potential of regenerative medicine. The current surge in scientific, preclinical, and clinical studies in regenerative therapies including stem cells and PRP has not only increased the therapeutic expectations, but also uncovered the scientific rationale behind them. Both the stem cell, as well as PRP-based therapies have imparted nerve cell regeneration through secretion of growth and nerve factors and anti-apoptotic activities. The pre-clinical studies have shown significant improvement in terms of restoring erectile functions through cell-based therapies in ED animal models, which could be improved through LI-ESWT by increasing cell viability, proliferation, and multilineage differentiation [144]. A recent study showed an improved therapeutic efficacy of Schwann cells with overexpressing GDNF in CNI-induced ED rats [145]. Thus, the overexpression of relevant growth factors may be targeted to promote rapid stem cell-mediated regeneration of damaged cavernosal nerves. Moreover, the stem cells in combination with non-surgical and pharmacological agents might prove to be a crucial therapeutic strategy for ED.
Similar to stem cells, PRP has also been widely studied for its regenerative potential, which is ascribed to its capability to secrete growth factors, cytokines, and ECM, thereby promoting migration, proliferation, stabilization, and differentiation of endothelial, fibroblast, and stem cells [146]. Therefore, the concentrations of platelet, cytokine, and growth factors need to be well established to achieve the optimal therapeutic impact of PRP [147]. Further, regenerative potential could be enhanced through combining both stem cells and PRP. However, to date, the studies on PRP and stem cells remain limited to establishing the clinical efficacy and safety for CNI-induced ED. Hence, extensive, multicenter, and large preclinical and clinical studies are required for the acceptance of these regenerative therapeutics.
