The mechanisms and potential of stem cell therapy for penile fibrosis

Abstract

| Fibrosis is often caused by chronic tissue injury leading to a persisting inflammatory response with excessive accumulation of extracellular connective tissue proteins. Peyronie's disease, urethral stricture and penile (corpora cavernosa) fibrosis are localized fibrotic disorders of the penile connective tissues that can substantially impair a patient's quality of life. Research over the past few decades has revealed the ability of stem cells to secrete a wide range of paracrine factors, a characteristic that could be exploited therapeutically to prevent and treat several inflammatory and fibrotic diseases. In preclinical studies, mesenchymal stem cells (MSCs) have proven to be the most effective and readily available type of stem cells for therapeutic use. An important advantage of MSCs is their ability to circumvent the immune system and function as immunomodulatory 'drug stores' to influence multiple cell types simultaneously. Many studies using stem cells have been applied exclusively to corpora cavernosa fibrosis owing to its well-established disease models. A plethora of preclinical data suggest the benefit of stem cells for use in penile fibrosis. However, their exact mechanism of action and optimal timing and mode of administration must be determined before clinical translation.

Simvastatin and the Rho‐kinase inhibitor Y‐27632 prevent myofibroblast transformation in Peyronie's disease‐derived fibroblasts via inhibition of YAP/TAZ nuclear translocation

“…The initial trigger for MFB formation can differ depending on its origin. For example, MFBs can develop from epithelial/endothelial‐to‐mesenchymal transition by TGF‐β1, IGF‐1, EGF and FGF2 . Other sources are circulating bone marrow‐derived fibrocytes which are activated by TGF‐β1 and endothelin‐1 .…”

“…For example, MFBs can develop from epithelial/endothelial‐to‐mesenchymal transition by TGF‐β1, IGF‐1, EGF and FGF2 . Other sources are circulating bone marrow‐derived fibrocytes which are activated by TGF‐β1 and endothelin‐1 . Tissue‐resident FBs undergo a transformation into MFBs through TGF‐β1 (released from inflammatory macrophages and the ECM), interleukin‐1b, platelet‐derived growth factor and reactive oxygen species .…”

“…Other sources are circulating bone marrow‐derived fibrocytes which are activated by TGF‐β1 and endothelin‐1 . Tissue‐resident FBs undergo a transformation into MFBs through TGF‐β1 (released from inflammatory macrophages and the ECM), interleukin‐1b, platelet‐derived growth factor and reactive oxygen species . In PD, the origin of MFBs is ill‐investigated; nonetheless, it seems that TGF‐β1 is the common denominator.…”

Ferrimagnetic Nanochains‐Based Mesenchymal Stem Cell Engineering for Highly Efficient Post‐Stroke Recovery

“…In recent years, stem‐cell‐based therapies opened a novel avenue for post‐stroke treatments. Among those stem cells, adult stem cells such as mesenchymal stem cells (MSCs) that are easy to isolate, less immunogenic, and more ethically feasible, are widely regarded as a promising candidate for post‐stroke therapy . In particular, MSCs are capable of migrating to the ischemia cerebrum and have the ability to secrete a wide range of paracrine factors, including brain‐derived neurotrophic factor (BDNF) .…”

What role do pharmaceuticals play in the treatment of Peyronie’s disease and is there a need for new emerging drugs?

“…This is likely to be one of the reasons why target-based therapeutic strategies have mostly failed, not only in fibrosis but also in drug discovery in general, where fewer successful drugs are discovered via this approach. This could explain the up rise of stem cell research, since mesenchymal stem cells can act as a local 'drug store', affecting multiple targets simultaneously [12]. While Scannell and colleagues provide an excellent insight into the productivity crisis in drug development [13], the approach for drug discovery needs to be taken into consideration.…”