REVIEWS

Platelet-Rich Plasma and Cellular Therapies for Sexual Medicine and

Beyond
Ethan L. Matz, MD, Kyle Scarberry, MD, and Ryan Terlecki, MD

ABSTRACT

Introduction: Efforts to understand and unlock the body’s potential for regeneration have increased dramatically
in recent years. So-called “biohacking” hopes to improve functionality and reverse disease processes.
Objectives: This review will seek to summarize the available data for the use of platelet-rich plasma, cellular
therapies, and other novel therapeutics within sexual medicine.
Methods: The PubMed database search was performed using the keywords “Stem cell therapy in Erectile
dysfunction (ED)”, “Gene therapy in ED”, “Novel therapeutics for ED”, and “Biohacking”. Popular news ar-
ticles for regulation of stem cell therapy were reviewed.
Results: Research efforts have managed to produce an array of novel therapeutics, including stem cell therapy
and platelet-rich plasma. Although the use of these items has been largely focused within specialties other than
urology, applications involving sexual medicine have been documented and appear to be increasing.
Conclusion: Despite evidence of these technologies being adopted within clinical practices as revenue-generators,
quality data to support efficacy are quite limited. Matz EL, Scarberry K, Terlecki R, Platelet-Rich Plasma and
Cellular Therapies for Sexual Medicine and Beyond. Sex Med Rev 2020;XX:XXXeXXX.
Copyright
2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Key Words: Cellular Therapies; Platelet Rich Plasma; Stem Cell Therapy; Men’s Health

INTRODUCTION interest as a way to “biohack” the human body in attempts to

One of the quintessential capabilities of the human body is the mitigate and potentially reverse disease processes. “Biohacking”
ability to heal the damage of everyday life. Cellular repair is or “body hacking” is an attempt to change or enhance the body’s
critical. Understanding and harnessing these capabilities for functionality.8 Platelet-rich plasma (PRP) is composed of highly
guided restoration of form and function is an area of avid interest concentrated platelets and plasma proteins produced from the
in medicine. Autologous transplant is especially interesting as it centrifugation of whole blood.9 Platelet-rich therapies are
eliminates the need for antirejection therapy.1 Autologous ther- increasingly being used in a wide range of medical special-
apies have been experimentally applied in fields such as ortho- ties.10e14 With PRP, artificial activators such as thrombin or
pedics, dermatology, plastic surgery, and urology.2e4 calcium chloride can be used to form platelet-rich fibrin matrix
(PRFM), a form of platelet-rich therapeutic that allows a more
Platelets are one of the body’s most potent actors in recovery prolonged release of factors over time.15
from injury. They are anucleated cells that are produced by
megakaryocytes, which contain a variety of factors including: Platelets are integral to wound healing and proper tissue
growth factors, chemokines, cytokines, and more.5 These regeneration.16 There are 4 different general preparations of
anucleated cells serve as “first responders” after insult and can PRP: pure PRP, leukocyte and PRP, PRFM, and leukocyte and
start a pathway to tissue regeneration.6 The exact mechanism of PRFM.17 To produce PRP, blood is drawn, and an anticoagulant
this is complex and the subject of other reviews; however, acti- is added. PRP may use a variety of anticoagulants, including
vated platelets release proteins favoring wound healing and tissue sodium citrate, ethylenediaminetetraacetic acid, or anticoagulant
regeneration.7 Thus, they have been a target of significant citrate dextrose.18 That mixture is then centrifuged and separated
into 3 layers, platelet-poor plasma, PRP, and red blood cells. The
red blood cells are then discarded and the mixture centrifuged
Received April 22, 2020. Accepted July 13, 2020.
again. The final product is the PRP layer with a small amount of
Department of Urology, Wake Forest School of Medicine, Winston-Salem,
NC, USA
platelet-poor plasma.15 There have been many publications of
the net gain in platelets in the final formulation, but it is likely
Copyright ª 2020, International Society for Sexual Medicine. Published by
Elsevier Inc. All rights reserved. about 2x higher than whole blood and has an elevated volume of
https://doi.org/10.1016/j.sxmr.2020.07.001 restorative cytokines.19

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2 Matz et al

After success in other fields of medicine, PRP has been used in outcomes.31 In osteoarthritis, studies propose that intraarticular
urology in attempts to enhance corporal (erectile) function and PRP injections act in an anti-inflammatory process and not in
even to bolster urethral coaptation.20 However, such studies are direct cartilage repair.32 Riboh et al found that leukocyte-poor
limited by low patient numbers from which to draw firm con- PRP leads to improved functional outcomes as compared to
clusions. Similarly, this potential therapeutic has been applied for injection of placebo or hyaluronic acid into the affected joint.33
clitoral injections in hopes of improving sexual enjoyment.21 PRP has been studied for other maladies involving fractures,
Stem cell therapy (SCT) is a broad descriptor for treatments hamstring injuries, patellar and Achilles tendinopathies, lateral
attempting to use multipotent cells of various origins to augment epicondylitis, and ligament injuries of the knee and elbow.2
the body, either through differentiation to a desired cell type, Wang and Rodeo provided grades of recommendation for PRP
direct modulation of body responses toward restoration, or a across various orthopedic conditions.2 However, they noted the
paracrine effect whereby other cells are stimulated to facilitate a overall quality of research is lacking.
favorable healing response.22 While these cells can be drawn Recently, PRP has become increasingly popular in the fields of
from various sources, adipose-derived stem cells (ADSCs) have dermatology, plastic surgery, and among disciplines seeking to
been increasingly used in recent years.23 Therapies involve encourage tissue regeneration and wound healing.28 In a study
aspirated portions of adipose that have been digested (chemically on hair thinning and alopecia, Takikawa et al demonstrated that
and/or mechanically) to a liquid derivative (stromal vascular PRP with or without dalteparin protamine microparticles facili-
fraction) and injected intracorporally in hopes of improving male tated hair growth.34 This was evaluated through scalp biopsies to
erectile function. A number of animal models such as those of determine cross-sectional hair counts.34 There are various studies
Qui et al and Fandel et al have shown that stromal vascular involving scar and scar revisions. Regarding acne scars, there are
fraction injected at the time of cavernous nerve injury is associ- several randomized controlled studies that demonstrate that PRP
ated with improved intracorporal pressures and erectile func- applications after CO2 laser or resurfacing lead to improved
tion.24,25 They also found that stromal cellederived factor-1 is clinical appearance of the scar and decreased erythema and edema
responsible for attracting ADSCs to the site of injury.24,25 as compared to laser or resurfacing alone.4,35 In dermatology,
Despite popularity and promotional efforts, such therapies also PRP has been investigated for uses including dermal augmenta-
lack the desired level of benefit, quantification of cellular content, tion, infraorbital dark circles, facial skin rejuvenation, and striae
and sufficient oversight.26 This has prompted a statement from distensae.15
the Sexual Medicine Society of North America in regard to the In urology, clinicians have trialed PRP for a variety of clinical
scope of application. conditions. The most robust animal model data come from the
This review will aim to provide an updated account of the erectile dysfunction (ED) literature. One study suggests that
published literature relative to the use of cellular therapies such as topical administration of PRP after injury to the cavernous nerve
PRP and SCT in sexual medicine. We will highlight parallel areas in rats may result in enhanced erectile functional recovery.36
of investigation in other fields, as the gains seen elsewhere may Another rodent study by Wu et al demonstrated that intra-
prompt new directions within urology. corporal injection of PRP optimized for the greatest concentra-
tion of platelet-derived growth factor had an improvement in
erectile function recovery as measured by intracorporal pressure
PLATELET-RICH PLASMA and immunofluorescent nerve staining.37 This study was limited
PRP was first used in the field of hematology in the 1970s to by using individual growth factors as indicators.37
concentrate platelets for transfusion.27 Its therapeutic utility was For stress urinary incontinence (SUI), there is no evidence in
then adapted to maxillofacial surgery, where its adherence either animal models or humans as to the efficacy of PRP.
properties along with anti-inflammatory characteristics and po- Nikolopoulos et al examined the evidence and hypothesizes that
tential to stimulate cell proliferation made it desirable.28 Soon PRP’s “adhesive, healing, and hemostatic” properties could be
after, PRP became popular in musculoskeletal specialties and restorative to the pubourethral ligament in patients with SUI.38
sports medicine.29 It should be noted that a critical analysis of A single animal study exists using a rat model for Peyronie’s
PRP studies across disciplines, through either randomized trials disease (PD), in which intratunical PRP injection was shown to
or meta-analysis, is exceedingly difficult given the varied prepa- create fibrosis similar to current injection protocols for induction
ration and concentration of the injected therapeutics. In addi- of PD.39 This raises the question of whether application of PRP
tion, platelet yield from individual products can vary.19 may run counter to therapeutic goals. However, repeated
Saltzman et al performed a meta-analysis on the use of PRP in microtrauma to the tunica albuginea can lead to fibrosis and PD
arthroscopic repair of rotator cuff injuries and found no signifi- independent of PRP.40
cant benefits on rates of repeat tearing or clinical outcomes.30 Human studies of PRP in urology are extremely limited. No
These outcomes included clinical indices, subjective measures, true efficacy studies exist. A single study examines the safety of
and rate of complications. PRP has been investigated in a large the injection of PRP for a variety of urologic conditions. In this
number of muscular and tendinous injuries with mixed study, 17 patients with ED, PD, ED þ PD, or SUI received PRP

Sex Med Rev 2020;-:1e6

Platelet-Rich Plasma and Cellular Therapies for Sexual Medicine and Beyond 3

injection.20 Intracavernosal injection of PRFM was performed in of single-nucleotide polymorphisms, and enhanced bacterial
men with ED (n ¼ 4), and PRFM injection directly into PD detection.55 Relative to ED, a review by Wang and Podlasek
plaques (n ¼ 11) was performed under ultrasound guidance. described 4 potential uses of nanotechnology.56 These included
Submucosal injection of PRFM was performed cystoscopically in topical delivery of drugs for on-demand improvement in erectile
one female with SUI (n ¼ 1). Results showed this appeared to be function, injectable gels to prevent morphological changes after
safe and feasible, with no major adverse events reported. 3 men prostatectomy, hydrogels to promote cavernous nerve regenera-
were noted to have mild pain at the injection site, and mild tion, and encapsulation of drugs to improve efficacy in disease
penile bruising was noted in one. Mean follow-up duration was management.56
15.5 months. While efficacy was reported, including subjective Low-energy shockwave therapy is offered clinically by many
curvature reduction in 4 of 5 men with PD and modest providers but remains under investigation with what appear to be
improvement in ED questionnaire results (International Index of promising results. The mechanism is thought to be “super
Erectile Function-5), the study was too small for meaningful healing” in response to microinjury from shockwaves. The results
statistical analysis or conclusion. of low-energy shockwave therapy in a rat model have been well
According to Scott et al, PRP is already in use in 19 countries with established.57e60 A meta-analysis conducted by Man and Li
a total of 683 providers using it worldwide.41 There is, however, a evaluated outcomes of low-intensity extracorporeal shock wave
paucity of good data for PRP in a variety of fields.42 There does exist therapy (Li-ESWT) among patients with ED.61 The study
some data to suggest very few adverse effects from PRP injection, and evaluated 637 patients from 9 studies and found that Li-ESWT
there is logic to support promise as a potential therapeutic. Therefore, resulted in modest but statistically significant improvement in
it seems reasonable and worthwhile to conduct appropriately pro- International Index of Erectile Function (mean difference 2.54,
tocoled prospective studies or randomized trials to examine the 95% confidence interval, 0.83e4.25; P ¼ .004) and Erection
therapeutic effects of PRP in multiple urologic conditions. Hardness Scale scores.61
Gene therapy uses injections of specific genes via a viral vector.
STEM CELL THERAPY This has potential in a variety of urologic conditions. In ED,
genes in the erectogenic pathway and vascular regenerative genes
SCT is still largely viewed as an enigma, with the exact are being targeted.1 Viral vectors targeting the various isoforms of
mechanism of benefit unknown.22 Mesenchymal stem cells nitric oxide synthase have aimed at improving erectile function.
(MSCs) arise from mesoderm and are capable of both self- Targets include nitric oxide synthase, pigment epithelium-
renewal and differentiation into a variety of lineages.43 MSCs derived factor, and vascular endothelial growth factor.62 Unfor-
can be procured from a number of sources including fat tunately, gene therapy and genetic biohacking, which historically
(ADSCs), bone marrow stem cells, placental stem cells, and was only a scientific endeavor, is now more accessible to parties
urine-derived stem cells.44e48 A number of animal models of ED lacking the appropriate understanding and oversight. This makes
have been evaluated with the various stem cell subtypes. Models it more susceptible to pseudoscientists.63
exist for examination of ED because of various etiologies
including neurogenic, vascular, diabetogenic, aging, and castra-
tion. In addition, there are limited clinical trials that evaluate PROCEEDING WITH OPTIMISM AND CAUTION
stem cells for ED. These studies had limited enrollment and were
underpowered to allow for interpretation of significant efficacy. The aforementioned novel therapeutics may hold promise for
Safety was assessed in these studies at follow-up by visual in- multiple disease states where truly effective options may be
spection of injection sites and subjective adverse event limited. Many of these disease states have therapeutics solely
reporting.49e52 According to clinicaltrials.gov, there are currently designed for management.64 Some of the options discussed could
212 trials using MSCs; however, there are no purely urologic potentially help reverse disease. However, the attractive nature of
studies within the United States. While the scope of application alternative therapies among consumers and the limited regulatory
of SCT within urology has been largely focused on ED, other oversight creates ample opportunity for commercial entities to
pathologic conditions may represent attractive targets. Applica- market poorly tested and unverified products.65 Indiscriminate
tion of MSCs appears to result in an antifibrotic effect by un- direct-to-consumer marketing has become commonplace, even
known mechanisms, which could be beneficial for urethral to the point of obtaining prescription medication for ED without
stricture disease.53 In fact, animal research has suggested that physical examination and evaluation that may uncover serious
stricture formation may be ameliorated by injection of human conditions (eg, diabetes, hypertension).66 Web-based services
ADSCs.54 (eg, getroman.com, hims.com) offer convenience for affected
men, but these individuals have the ability to present themselves
as otherwise healthy, even when that may be far from the truth.
OTHER THERAPEUTIC DIRECTIONS Predatory practices among select men’s health clinics have
Nanomedicine is using nanoscale (1e1000 nm) materials as been reported across numerous popular news outlets.67 This has
therapeutics. Nanotechnology can be used for imaging, detection become a multibillion-dollar industry in the United States, and

Sex Med Rev 2020;-:1e6

4 Matz et al

men may be subjected to overpriced, unevidenced, inappro- carbon dioxide laser treatment of atrophic acne scars. Der-
priate, and potentially dangerous interventions.68 For providers matol Surg 2014;40:152-161.
looking to advance the field and to protect their patients, it is 5. Rendu F, Brohard-Bohn B. The platelet release reaction:
conceivable that financial interests could derail interest in ther- Granules’ constituents, secretion and functions. Platelets
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The position statement of the Sexual Medicine Society of North 6. Jurk K, Kehrel BE. Platelets : Physiology and Biochemistry.
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man data on restorative therapies (PRP, MSC, Li-ESWT) are 7. Nurden AT. Platelets, inflammation and tissue regeneration.
limited and “data conclusively validating these mechanisms are Thromb Haemost 2011;105:13-33.
currently lacking.”69 8. Yetisen AK. Biohacking Trends Biotechnol 2018;36:744-747.
9. Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and
its clinical application in cartilage repair. Arthritis Res Ther
CONCLUSION
2014;16:204.
Moving forward in our delivery of care within men’s 10. Andia I, Maffulli N. Platelet-rich plasma for managing pain and
health, it is essential that we maintain focus on optimizing inflammation in osteoarthritis. Nat Rev Rheumatol 2013;
wellness in a manner that is safe, efficient, and cost- 9:721-730.
effective. While cellular therapies seem to hold great 11. Jiritano F, Serraino GF, Rossi M, et al. Ventricular assist device
promise, they also lack sufficient evidence in most instances. driveline infection: treatment with platelet-rich plasma. Ann
Delivery of novel therapeutics should be performed Thorac Surg 2013;96:e37-e38.
responsibly and by providers specifically trained in men’s 12. Marck RE, Middelkoop E, Breederveld RS. Considerations on
health, rather than rogue tourists from commercial entities the Use of platelet-rich plasma, specifically for Burn treat-
or unrelated disciplines. Sexual health providers in particular ment. J Burn Care Res 2014;35:219-227.
should seek to collaborate with established basic scientists to 13. Schiavone G, Raskovic D, Greco J, et al. Platelet-rich plasma
conduct well-designed clinical trials. Such efforts should for androgenetic alopecia: a pilot study. Dermatol Surg 2014;
offer the best chance of identifying viable treatment options 40:1010-1019.
for the future. 14. Zhou B, Ren J, Ding C, et al. Protection of colonic anastomosis
Corresponding Author: Ryan Terlecki, MD, Wake Forest with platelet-rich plasma gel in the open abdomen. Injury
2014;45:864-868.
School of Medicine, Department of Urology, 1 Medical Center
Blvd, Winston-Salem, NC 27157, USA. Tel: 336-716-3270; 15. Leo MS, Kumar AS, Kirit R, et al. Systematic review of the use
Fax: 336-716-5711; E-mail: [email protected] of platelet-rich plasma in aesthetic dermatology. J Cosmet
Dermatol 2015;14:315-323.
Conflict of Interest: R.T. receives grant support and is a consultant 16. Werner S, Grose R. Regulation of wound healing by growth
for Boston Scientific. E.L.M. and K.S. have no conflicts to factors and cytokines. Physiol Rev 2003;83:835-870.
disclose. 17. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classifi-
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Funding: None.
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Biotechnol 2009;27:158-167.
STATEMENT OF AUTHORSHIP 18. Do Amaral RJFC, Da Silva NP, Haddad NF, et al. Platelet-rich
plasma obtained with different anticoagulants and their effect
Ethan L. Matz: Writing - Original Draft, Writing - Review &
on platelet numbers and mesenchymal stromal cells Behavior
Editing, Investigation; Kyle Scarberry: Writing - Review & in Vitro. Stem Cells Int 2016;2016.
Editing; Ryan Terlecki: Conceptualization, Investigation,
19. Matz EL, Vanhorn T, Terlecki RP, et al. MP59-19 CYTOKINE
Writing - Review & Editing.
analysis OF platelet rich plasma for use IN urologic thera-
peutics. Journal of Urol 2019;201:e868.
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