The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie's Disease: A Systematic Narrative Review

Abstract

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.

Keywords: erectile dysfunction; penile diseases; penile diseases therapy; penile induration; physiopathology; stem cell transplantation; therapy.

Figure 1

PRISMA flowchart in searching the original articles.

Figure 2

Inflammatory mechanism in PD. After the inflammation is activated, the activated macrophages and formation of fibrin will initiate the cascades up-regulating the fibroblasts transformation, and subsequently lead to fibrosis.

Figure 3

(A) The current preclinical studies of applying ADSCs in treating PD. In published literature, only the downstream pathways were discussed. Several pivotal impacts by ADSCs were not yet addressed, such as macrophages polarization, free radicals, oxidative stress, and NF-κB. (B) The abbreviated illustration of how ADSCs alter the immunological microenvironment of PD. In the published preclinical studies, the most mentioned immunological microenvironments changes by ADSCs were inhibiting TGF-β1/Rho/ROCK, and inhibiting TGF-β1/Smad2. Moreover, the increased TIMPs and decreased MMPs were reversed by the ADSCs.