ESSM Newsletter # 39

9 ESSM Today Still round the corner there may wait, a new road or a secret gate: Stem cell therapy for Peyronie’s disease by Fabio Castiglione and Asif Muneer Stem Cell therapy for Fibrosis Fibrosis is defined by an excessive accumula- tion of extracellular connective tissue proteins (extracellular matrix (ECM)) such as collagen, elastin and fibronectin. Typically, ECM aggre- gation is an essential and reversible phase of the wound healing process (1). It can however evolve into a gradually permanent fibrotic re- action if the tissue injury is grave, repetitive, or in case the wound-healing process itself becomes deregulated. Fibrosis represents the conclusive, typical pathological consequence of many chronic inflammatory disorders and can lead to a progressive loss of organ function (2). Adult mesenchymal stem cells (MSCs) are classified as multipotent stem cells which dif- ferentiate into several types of mesenchymal cells. Until recently this property had only been studied for its direct medical implications and therapeutic uses. However, MSCs release a wide spectrum of regulatory and trophic factors (growth factors, cytokines and chemokines). This suggests a paracrine effect as “site- regulated drugstores” in vivo and can have an effect on tissue even if they do not engraft or differentiate (3). In the last decades, research- ers have tried applying SCs by exploiting their immune-regulatory properties to several thera- peutic scenarios. A few examples include graft- versus-host disease (GVHD) in bone marrow transplantation, multiple sclerosis, brain and spinal cord injury, arthritis, myocardial infarction and Crohn's disease (4). More importantly, over the last few decades, there is an accumulation of evidence that SCs play a major role in normal wound healing. They accelerate wound contraction, process and in- crease the quality of the tissue, counteract healing anomalies and reduce the amount of ECM produced. The latter contributes to a better cosmetic result of the scar tissue (5). Supported by this evidence, it is unsurprising that several studies were performed evaluating the efficacy of SCs in treating fibrotic disorders with positive results especially for Lung and liver fibrosis (6,7). The anti-fibrotic properties of SCs are not yet properly understood and are a topic of inten- sive research. A growing body of evidence, however, suggests SCs act via immunomodu- lation, ROS neutralization and angiogenesis (8–10) (fig.1). Fabio Castiglione M.D. FECSM Department of Urology and NIHR Biomedical Research Centre University College London Hospital London, UK dr.castiglione.fabio@gmail.com Asif Muneer MD FRCS (Urol) Department of Urology and NIHR Biomedical Research Centre University College London Hospital London, UK mramuneer@gmail.com Fig. 1: Antifibrotic properties of MSCs MSCs act by modulating all the steps of the wound healing exploiting their immunomodulation, ROS neutralization and angiogenesis properties. Stem cell therapy for PD – what the evidences really says… Peyronie’s disease (PD) represents localized connective penile tissue disorders character- ized by changes in collagen composition of the tunica albuginea (TA) (11). The consequences of these conditions can enormously impair the patient’s sexual quality of life by causing curva- ture of the penis, impairment of erectile func- tion and erection-related pain (11). Commonly, PD is classified into an acute (or inflammatory) phase and a chronic (or stable) phase. During the chronic phase, since the inflammatory process has settled, pain is absent and the curvature and TA fibrosis are stable. In the last 2 decades, several antifibrotic drugs have been tested as treatment for PD. Unfortunately, except for col- lagenase, none of these drugs exhibit sufficient therapeutic benefit (12). To date 3 studies had tested the mesenchy- mal stem cells local injection as therapy for PD (13–15) in animals. Castiglione et al. (13) were the first to show the efficacy of adipose derived stem cells (ADSCs) in PD. They injected xenogeneic (hu- man) ADSCs into the TA of rats with experimen-