Background: This pilot study was used to evaluate safety and subjective outcomes in a small series of Peyronie’s disease patients using a combination of autologous stromal vascular fraction (SVF) and penile shock wave treatments. SVF can be procured and deployed into Peyronie’s plaques, enabling the surgeons to procure and mobilize significant numbers of both adult mesenchymal stem cells and anti-inflammatory cytokines released from the adipose collagen matrix after collagen digestion. Penile shock wave therapy stimulates targeted tissues and may activate stem cells found in the SVF and promote healing and fibrosis mitigation. Methods: SVF isolated from lipoaspirate was deployed by injection into 11 patients with Peyronie’s plaques in combination with a series of shock wave treatments. Subjective outcomes tests performed at baseline and at 6 months included the Erectile Hardness Grading Score and the Peyronie’s Disease Questionnaire (Questions 1–6). Results: All patients noted subjective improvement in curvature and subjective reduction in plaque size. Seven patients reported improvement in erectile function. Mean Erectile Hardness Grading Score increased from 2.7 to 3.5, and mean Peyronie’s Disease Questionnaire scores decreased from 15.0 to 8.7. Conclusions: SVF is known to have scar mitigation, anti-inflammatory, immunomodulatory, and regenerative effects, and it has been used for a variety of conditions on an investigational basis. SVF containing mesenchymal stem cells can be procured in a closed surgical system from lipoaspirate in a same-day setting and deployed directly into Peyronie’s plaques in combination with penile shock wave therapy resulting in plaque mitigation. (Plast Reconstr Surg Glob Open 2016;4:e631; doi: 10.1097/ GOX.0000000000000622; Published online 2 March 2016.)

 

Peyronie’s disease is considered a hypertrophied scar of the tunica albuginea and affects millions of American men. Surgical repair is associated with penile scarring, penile shortening, and worsening of erectile dysfunction (ED) in many cases. Nonsurgical therapeutic options are limited, and results do not exceed placebo for most remedies. Evidence shows that there is no benefit with respect to deformity reduction in Peyronie’s disease with any oral therapy, including vitamin E, potassium aminobenzoate, colchicine, tamoxifen, and carnitine.1

Double-blind studies on intralesional verapamil and interferon have failed to demonstrate any significant differences/improvements in penile deformity, pain, plaque softening, or sexual function, and intralesional steroids have not shown objective therapeutic benefit.
1 Intralesional collagenase Clostridium histolyticum (Xiaflex, Auxilium Pharmaceuticals, Chesterbrook, Penn.) injections are the first Food and Drug Administration-approved treatment for Peyronie’s disease (PD), and the studies demonstrate efficacy of the treatment, but there have been documented cases of corporal rupture, penile hematoma, and penile pain.

2. There has been recent anecdotal interest in biologic therapies including the use of platelet-rich plasma to treat Peyronie’s disease, but there is a paucity of outcomes data. Platelet-rich plasma contains many antiinflammatory cytokines, but it is relatively deficient in cellular components. Stromal vascular fraction (SVF) obtained from the enzymatic digestion of liposuction fat is known to have regenerative, antiinflammatory, scar mitigating, and immunomodulatory properties. Pursuing an SVFbased cell therapy option for PD requires a deeper understanding of the cellular basis of Peyronie’s disease. Excessive amounts of fibrin were identified in these plaques in 1997 by Somers and Dawson.

3. A deeper understanding of the cellular basis of Peyronie’s plaques came a few years later with the understanding that there was oversecretion of collagen associated with
the excessive transforming growth factor β1 (TGF- β1)–mediated fibroblast conversion into myofibroblasts. These cells that are a normal part of healing are expected to undergo apoptosis when healing is complete, and loss of the apoptotic signal appears to be instrumental in Peyronie’s formation.

4. These findings in addition to the presence of reactive oxygen species (ROS) contribute to the thick scarring, curvature, and ED associated with Peyronie’s disease.

5. Through technologic advances, we are currently able to isolate autologous SVF from 50cm3 of adipose tissue lipoaspirate in a sterile, closed system within 2 hours in the operating room. SVF isolated from the connective tissue associated with subcutaneous fat and blood vessels is known to contain adult mesenchymal stem cells (MSCs), T regulatory cells, endothelial precursor cells, preadipocytes, antiinflammatory M2 macrophages, and numerous cytokine growth factors.

6. Recently, there is a plethora of anecdotal evidencebased information to suggest that MSCs may have significant beneficial use for a variety of autoimmune, inflammatory, and degenerative conditions.

7–12. There is also a large veterinary experience using SVF showing safety and efficacy.13 The antiinflammatory cytokines in SVF may accelerate healing and mitigate collagen overdeposition activity associated with Peyronie’s disease. The literature regarding the cellular and molecular differences in inflammation between scar-free wound healing and scar-forming wound healing indicates that scar formation may be prevented by inflammatory regulation.

14. Low-intensity acoustic shock waves have been used to treat Peyronie’s disease, and positive results have been well described in the urologic literature.

15,16, Shock wave technology has been previously combined with mesenchymal cell therapy in the treatment of cardiac disease, and the combination has been shown to be superior to either therapy alone for improving ejection fraction and reducing infarct size.17 Regenerative cells in SVF can be activated by cytokine signals released from tissue that is diseased, damaged, or inflamed. Low-intensity shock waves create controlled microtrauma that is expected to be able to mimic these conditions and may help tropism homing and activation of stem cells and other resident progenitor cells.

For more information on this trial (including the references described above) please click here.