Reviewing the evidence for shockwave- and cell-based regenerative therapies in the treatment of erectile dysfunction

Abstract

Erectile dysfunction (ED) is both a common and complex disease process. Existing ED treatments do not always achieve adequate results. There is clinical interest in employing regenerative therapies, including low-intensity extracorporeal shockwave therapy (Li-ESWT), platelet rich plasma (PRP), and stem cell therapy (SCT), in the treatment of ED as adjunct or alternative treatments. Here, we present evidence for emerging shockwave- and cell-based regenerative therapies for the treatment of ED following a thorough review of the existing PubMed literature pertaining to Li-ESWT, PRP, and SCT in relation to the treatment of ED. Li-ESWT causes microtrauma in tissue that hypothetically upregulates angiogenesis and recruits stem cells. Several large-scale systematic reviews and meta-analyses have reported that Li-ESWT improved ED in humans. Additionally, evidence has commenced to show that Li-ESWT may be effective against two recognized and complex etiologies of ED: diabetic and neurogenic. PRP delivers an autologous sample rich in growth factors to damaged tissue. Animal model studies have demonstrated improved erectile function recovery as well as preservation of cavernous nerve axons. Studies with PRP in humans are limited. SCT utilizes the regenerative potential of stem cells for healing of damaged tissue. In the treatment of ED, SCT has been used in the setting of diabetic and post-prostatectomy ED. Results of human studies are varied, although SCT treatments did result in increased erectile rigidity with some patients recovering the ability to achieve penetration. While these regenerative therapies show potential to augment the current treatment regimen for ED, there is a paucity of evidence to support the safety and efficacy of these treatments. Further research is necessary to define the role of these alternative therapies in the treatment of ED.

Comparison of the efficacy of low‐intensity shock wave therapy and its combination with platelet‐rich plasma in patients with erectile dysfunction

“…The PRP‐treated group exhibited a significantly greater number of preserved myelinated cavernous neural axons at 1 month as compared to the non‐PRP‐treated group. These results support the conclusion that PRP increases the number of myelinated axons, thus facilitating the recovery of erectile function (Drury et al., 2021; Raheem et al., 2020). Similarly, the Group 2 patients in our study reported that in repeated PRP injections, the sensation of sensitivity and pain in the penile area increased as compared to the previous injection, despite application of the same local anaesthetic.…”

“…The PRP-treated group exhibited a significantly greater number of preserved myelinated cavernous neural axons at 1 month as compared to the non-PRP-treated group. These results support the conclusion that PRP increases the number of myelinated axons, thus facilitating the recovery of erectile function (Drury et al, 2021;Raheem et al, 2020).…”

“…These GFs play an important role in natural wound healing, vascular remodelling and inflammatory and immune responses (Galliera et al., 2012). PRP is a well‐described, platelet‐based treatment that is prepared by the centrifugation of the patient's own blood (Drury et al., 2021). The application of PRP to the site of the cavernous nerve (CN) injury has neuromodulatory effects on the regeneration of the CN and recovery of the erectile function (Campbell et al., 2020; Ding et al., 2009).…”

Cavernous Nerve Injury Resulted Erectile Dysfunction and Regeneration

“…Thus, although the mechanism of action of stem cells in the treatment of ED in cavernous nerve injury is becoming clear, there is still controversy about the possible role of stem cells in the treatment of ED without an acute pathogenetic cause. Some of the stem cell studies described above also illustrate an exciting avenue for regenerative medicine between gene therapy and stem cell applications, as stem cells are increasingly being used as vectors to deliver genes to desired tissues [ 58 , 59 ].…”

Efficacy of Penile Low-Intensity Shockwave Therapy and Determinants of Treatment Response in Taiwanese Patients with Erectile Dysfunction

“…Following the seminal work of Vardi et al demonstrating the applicability of Li-ESWT in andrology [7,8], there is accruing evidence of the therapeutic benefit of Li-ESWT in patients with ED [8][9][10]. Previous studies have associated the observed therapeutic benefit with the intrinsic ability of Li-ESWT to up-regulate growth factors, promote endothelial progenitor cell proliferation and activation, induce neovascularization, increase the production of nitric oxide, elicit tissue reperfusion and regeneration, and consequently improve erectile function [11][12][13].…”