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Response to the Commentary on: Safety and feasibility of percutaneous needle tunneling with platelet-rich plasma injections for Peyronie’s disease in the outpatient setting: a pilot study

International Journal of Impotence Research volume 36, pages 299–300 (2024)Cite this article

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We thank our Turkish colleagues on commenting our study [1, 2]. They started off with an impeccable summary of our work then moved on explaining how several fibrotic mediators in Platelet-Rich Plasma (PRP) especially TGF-β can induce healing complications like scar tissue and fibrosis [2]. They mentioned that the supplementation of certain antibodies can counteract this effect and/or by applying PRP purification methods can prevent fibrosis. Furthermore, they stated that percutaneous needle tunneling’s (PNT’s) traumatic effect can activate certain macrophages that can contribute to fibrosis.

The aim of using PRP is to stimulate the normal healing process, as, in addition to their role in hemostasis, platelets are involved in the regulation of tissue repair. When performing PNT to break the fibrotic plaques in patients suffering from Peyronie’s disease (PD), PRP is used to stimulate healing without inducing new fibrotic tissue formation. Platelet granules contain various active substances (More than 300 according to Golebiewska et al.) and some of them are pro-inflammatory, as inflammation is part of the normal healing process [3]. However, in physiological healing, the inflammatory stage is transitory. The certified medical device used to prepare PRP in our study (RegenKit BCT-3, Regen Lab, Switzerland), allows the preparation of a standardized leukocyte poor PRP with virtually no red blood cells (RegenPRP) [4]. The effective depletion of those undesired blood cells in RegenPRP ensure avoidance of unregulated inflammatory reactions at the site of injection. The platelet concentration factor in RegenPRP is around 1.6 times the baseline value in whole blood. As the physiological platelet/plasma ratio is maintained, such PRP stimulates the healing in respect to physiological tissue homeostasis. In addition, platelets are fully functional in RegenPRP, hence the growth factors are released in an orchestrated manner in response to local signals and according to the different steps of the healing process [3]. This is not the case when frozen/thawed PRP or PRP clot releasate are used, as it was the case in the Li and Tsai studies mentioned in the comment [5, 6]. In such products, the growth factors from platelets, but also from the leukocytes when present in the PRP, are released in bulk, hence in high dose and without regulation. The PRP used by Culha et al. on an animal model of PD was not characterized [7]. Nevertheless, the device used for its preparation (GLO-PRP kit, GloFin, Finland) is known to produce a pro-inflammatory leukocyte-rich PRP with a very high platelet concentration factor (4–9x) [8]. The fibrosis induced by this type of PRP in this study is probably due to its cellular composition, as fibrosis is the result of uncontrolled inflammatory reactions [9]. Contrary to leukocyte rich PRP, leukocyte poor PRP induces the transition of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages [10]. This physiological transition conducts to the granulation phase of the healing process. As for inflammation, the granulation phase should be regulated and transitory, in order to avoid excessive production of extracellular matrix proteins that could lead to fibrosis [11]. The transition to the remodeling phase leads to the resolution of the wound. On the contrary, a reversion from M2 to M1 macrophages is not desirable as this would lead to sustained inflammation and prevent healing [12].

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References

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Acknowledgements

We send our dearest appreciation and gratitude to Solange Vischer for the precious input.

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Authors and Affiliations

  1. Urology Division, Department of Surgery, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia

    Ahmed S. Zugail

  2. Department of Urology, Clinique Turin, Groupe Almaviva Santé, Paris, France

    Ahmed S. Zugail & Sébastien Beley

  3. Urology Division, Department of Urology, Faculty of Medicine, University of Ha’il, Ha’il, Saudi Arabia

    Muaath Alshuaibi

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Contributions

Research conception and design: AZ, MA, and SB. Data/information acquisition: AZ, MA, and SB. Drafting of the manuscript: AZ. Critical revision of the manuscript: MA and SB. Supervision: SB. Approval of the final manuscript: AZ, MA, SL and SB.

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Correspondence to Ahmed S. Zugail.

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Zugail, A.S., Alshuaibi, M. & Beley, S. Response to the Commentary on: Safety and feasibility of percutaneous needle tunneling with platelet-rich plasma injections for Peyronie’s disease in the outpatient setting: a pilot study. Int J Impot Res 36, 299–300 (2024). https://doi.org/10.1038/s41443-024-00874-x

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