madman
Super Moderator
Erectile Dysfunction (ED) is defined as the inability to achieve and maintain an erection sufficient for sexual intercourse. Available treatments for ED provide only symptomatic relief, which is for the most part temporary. Regenerative therapies such as Low-Intensity Shockwave, Platelet-Rich Plasma, and Stem Cell therapy can potentially provide a “cure” for ED by reversing the underlying pathology of ED rather than just treating the symptoms. Low-Intensity Shockwave therapy is the most evidence-based at this point and is thought to act by improving penile blood flow, repairing previous nerve damage, and activating stem cells. Stem Cell therapy takes advantage of the self-replicative potential of stem cells to create new corporal tissue, but also to recruit host cells and angiogenic factors to stimulate endogenous repair. Platelet-Rich Plasma therapy uses concentrated growth factors that already exist within the bloodstream to repair damaged nerves and increase penile blood flow. The use of combination restorative therapy may provide an additive or synergistic benefit greater than any one therapy alone because of its overlapping mechanisms of action on the penis but is a topic that remains to be studied.
LOW-INTENSITY SHOCKWAVE THERAPY (LISWT)
LOW-INTENSITY SHOCKWAVE THERAPY (LISWT) Shockwave therapy was first introduced to the field of Urology back in the 1970s aimed as a treatment for kidney stones [8]. LiSWT has more recently been adapted for use in the treatment of ED [3, 9]. It works by distributing shockwaves in a targeted, localized area of the penile shaft (Supplementary Video). The resulting trauma and stress to the tissue promotes neovascularization, improves progenitor cell activation, and overall increases blood flow to the penis [3, 5, 10].
PLATELET-RICH PLASMA (PRP)
PRP is autologous blood plasma with platelet concentrations that are 3–7 times greater than the typical plasma and several growth factors. It has been described as a treatment in multiple specialties including orthopedics [21], dermatology [22], and cardiothoracic surgery [23]. Recently studies have started to investigate the use of PRP for ED (Supplementary Video). Several growth factors are released from the platelets when activated after injection [24], and the most commonly studied are vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF). These growth factors have been shown to improve erectile function in preclinical models as well as early clinical studies [25–28]. VEGF mediated improvement in erectile function has been shown to work through the endothelial nitric oxide synthase (eNOS) pathway and PRP has also been shown to facilitate nerve repair and regeneration in animal models [25, 26].
*Currently, Ramasamy et al. at the University of Miami are conducting a study investigating the role of PRP in ED with an estimated enrollment of 80 participants and a placebo group. This study’s design and size address some of the flaws in the previous studies and are estimated to be complete in September of 2022 [30].
STEM CELL THERAPY (SCT) & STROMAL VASCULAR FRACTION THERAPY (SVF)
SCT involves isolation of Mesenchymal Stem Cells (MSCs) or Stromal Vascular Fraction (SVF), which is injected into the penile tissue to stimulate endogenous repair. MSCs are a unique population of adult stem cells that can be found scarcely throughout the body, and in higher concentrations in bone marrow, umbilical cord, and adipose tissue, among others [31]. MSCs have the potential for significant clinical benefit in ED through improving endothelial function [32]; improving blood flow to the penis [33, 34], or from local implantation of cells into corporal tissue, and reversal of damage via paracrine effects [35, 36].
SVF is comprised of a mixture of adipose-derived stem cells, endothelial precursor cells, and immunomodulatory cells which are obtained from abdominal fat tissue [37]. SVF can be given as an injection into the penile tissue to restore erectile function (Supplementary Video), however, the evidence to support its use as a clinical therapy is scarce compared to other regenerative therapy options
COMBINATION REGENERATIVE THERAPY
The idea of using two or more regenerative therapies to treat ED in the same patient is novel—only preliminary data has been presented at academic conferences to the urologic community. Despite there being a paucity of data on the subject, this approach merits discussion; if one were to “attack” ED with multiple therapies that each target different pathophysiological lead points, the sum benefit should be greater than that of each individual part. This might be especially relevant for men with a mixed subtype of ED that is challenging for the practitioner to treat and refractory to traditional monotherapy.
A WORD OF CAUTION
While regenerative ED therapies are exciting due to their potential for providing a “cure” for ED, there is not enough data to support their use in clinical practice. With the exception of LiSWT, very few RCTs exist that can attest to the efficacy of PRP, SCT, and SVF for treating ED. Similarly, while using a combination of regenerative therapies has a hypothetical promise for treating moderate to severe ED, it is a topic that is barely discussed in the literature, and more efforts are needed to promote this area of research in men’s health. Robust clinical trials are needed to discern if individual, as well as combination, has treatment efficacy compared to placebo. All forms of regenerative ED therapy that are offered should be disclosed as investigational only, and any treatment provided through these avenues should be in the context of IRB-approved studies.
LOW-INTENSITY SHOCKWAVE THERAPY (LISWT)
LOW-INTENSITY SHOCKWAVE THERAPY (LISWT) Shockwave therapy was first introduced to the field of Urology back in the 1970s aimed as a treatment for kidney stones [8]. LiSWT has more recently been adapted for use in the treatment of ED [3, 9]. It works by distributing shockwaves in a targeted, localized area of the penile shaft (Supplementary Video). The resulting trauma and stress to the tissue promotes neovascularization, improves progenitor cell activation, and overall increases blood flow to the penis [3, 5, 10].
PLATELET-RICH PLASMA (PRP)
PRP is autologous blood plasma with platelet concentrations that are 3–7 times greater than the typical plasma and several growth factors. It has been described as a treatment in multiple specialties including orthopedics [21], dermatology [22], and cardiothoracic surgery [23]. Recently studies have started to investigate the use of PRP for ED (Supplementary Video). Several growth factors are released from the platelets when activated after injection [24], and the most commonly studied are vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF), and fibroblast growth factor (FGF). These growth factors have been shown to improve erectile function in preclinical models as well as early clinical studies [25–28]. VEGF mediated improvement in erectile function has been shown to work through the endothelial nitric oxide synthase (eNOS) pathway and PRP has also been shown to facilitate nerve repair and regeneration in animal models [25, 26].
*Currently, Ramasamy et al. at the University of Miami are conducting a study investigating the role of PRP in ED with an estimated enrollment of 80 participants and a placebo group. This study’s design and size address some of the flaws in the previous studies and are estimated to be complete in September of 2022 [30].
STEM CELL THERAPY (SCT) & STROMAL VASCULAR FRACTION THERAPY (SVF)
SCT involves isolation of Mesenchymal Stem Cells (MSCs) or Stromal Vascular Fraction (SVF), which is injected into the penile tissue to stimulate endogenous repair. MSCs are a unique population of adult stem cells that can be found scarcely throughout the body, and in higher concentrations in bone marrow, umbilical cord, and adipose tissue, among others [31]. MSCs have the potential for significant clinical benefit in ED through improving endothelial function [32]; improving blood flow to the penis [33, 34], or from local implantation of cells into corporal tissue, and reversal of damage via paracrine effects [35, 36].
SVF is comprised of a mixture of adipose-derived stem cells, endothelial precursor cells, and immunomodulatory cells which are obtained from abdominal fat tissue [37]. SVF can be given as an injection into the penile tissue to restore erectile function (Supplementary Video), however, the evidence to support its use as a clinical therapy is scarce compared to other regenerative therapy options
COMBINATION REGENERATIVE THERAPY
The idea of using two or more regenerative therapies to treat ED in the same patient is novel—only preliminary data has been presented at academic conferences to the urologic community. Despite there being a paucity of data on the subject, this approach merits discussion; if one were to “attack” ED with multiple therapies that each target different pathophysiological lead points, the sum benefit should be greater than that of each individual part. This might be especially relevant for men with a mixed subtype of ED that is challenging for the practitioner to treat and refractory to traditional monotherapy.
A WORD OF CAUTION
While regenerative ED therapies are exciting due to their potential for providing a “cure” for ED, there is not enough data to support their use in clinical practice. With the exception of LiSWT, very few RCTs exist that can attest to the efficacy of PRP, SCT, and SVF for treating ED. Similarly, while using a combination of regenerative therapies has a hypothetical promise for treating moderate to severe ED, it is a topic that is barely discussed in the literature, and more efforts are needed to promote this area of research in men’s health. Robust clinical trials are needed to discern if individual, as well as combination, has treatment efficacy compared to placebo. All forms of regenerative ED therapy that are offered should be disclosed as investigational only, and any treatment provided through these avenues should be in the context of IRB-approved studies.
