The Activation of Humoral Immunity Causes Lower Urinary Tract Dysfunction Related with Prostate Through the Different Mechanism from the Prostate Volume
14 Aug 202516:3016:45
Chun-Hou LiaoTaiwanModeratorRegeneration Medicine in Urology - A Promising Future or Hoax?Regenerative medicine comprises therapeutic strategies aimed at restoring tissue structure and function, rather than merely alleviating symptoms. By deploying cells, biomaterials, bioactive molecules, or combinations thereof, these interventions stimulate the body’s intrinsic repair mechanisms. This paradigm extends beyond traditional symptomatic treatment, offering the potential for true self-healing and organ reconstruction—ultimately prioritizing cure over chronic disease management.
Cell-based therapy has emerged as a promising intervention for various urogenital disorders, including erectile dysfunction (ED), bladder dysfunction, and male infertility. Current clinical research primarily focuses on mesenchymal stem cells (MSCs), investigating their safety, tolerability, and preliminary efficacy. Although early-phase studies suggest functional benefits—such as improved hemodynamics and tissue regeneration—most programs remain in preclinical or early clinical stages. A critical limitation remains the lack of standardization in MSC source, dose, and delivery route.
Among alternative sources, human amniotic fluid-derived stem cells (hAFSCs) have shown particular promise. In preclinical models of cavernous nerve injury, hAFSCs demonstrated prolonged retention in penile tissue and in-situ differentiation into α-smooth muscle actin-positive corporal smooth muscle cells, effectively replacing damaged tissue and restoring function. These findings represent an encouraging step toward curative therapy. However, the mechanisms governing their in vivo behavior—such as engraftment, differentiation, and immunogenicity—will ultimately determine their clinical translatability and therapeutic stability. Whether cell-based approaches can evolve from experimental platforms into routine clinical care remains a central question.
Platelet-Rich Plasma (PRP)
Platelet-rich plasma (PRP) is an autologous biologic product enriched with supraphysiologic levels of platelets, growth factors, chemokines, and extracellular vesicles. Upon activation, PRP releases a bioactive cocktail that promotes angiogenesis, neuroregeneration, and antifibrotic remodeling—key processes in the restoration of urogenital tissues.
In rodent models of cavernous nerve injury, PRP has been shown to preserve corporal sinusoidal endothelial cells and axonal scaffolds, while restoring erectile hemodynamics. Clinical studies further support PRP's safety in humans and report variable but promising improvements in IIEF scores following intracavernous injection. Nevertheless, the therapeutic response appears heterogeneous, likely influenced by patient factors, PRP preparation techniques, and injection protocols. Beyond ED, PRP has shown potential in other urologic indications such as stress urinary incontinence (SUI), interstitial cystitis/bladder pain syndrome (IC/BPS), and chronic pelvic pain, where it may contribute to tissue regeneration and symptom relief. However, broader adoption will require the establishment of individualized blood-quality metrics, standardized preparation methods, and randomized controlled trials demonstrating durable benefit.
Emerging Regenerative Strategies
Beyond cell-based and autologous biologics, a suite of innovative regenerative technologies is progressing from bench to bedside. These include:
Energy-based devices such as low-intensity extracorporeal shock wave therapy (Li-ESWT), which promotes neovascularization and tissue regeneration via mechanotransduction pathways.
Gene therapies, targeting dysfunctional or absent proteins in disorders like overactive bladder.
Smart biomaterials, capable of delivering cells or bioactive molecules in a controlled, responsive manner.
Extracellular vesicle (EV)-based therapeutics, which leverage cell-free vesicles derived from MSCs or urine-derived stem cells. These EVs carry signaling molecules (e.g., microRNAs, cytokines, growth factors) that mimic the paracrine effects of stem cells, offering a potentially safer and more scalable alternative to cell transplantation.
In preclinical models of ED and bladder dysfunction, EVs have demonstrated the capacity to promote smooth muscle regeneration, nerve sprouting, and fibrosis reduction, with functional improvements comparable to stem cell therapy.
Regenerative medicine has propelled the field of urologic tissue repair from theoretical promise to an early clinical reality. While substantial challenges remain—including the need for deeper mechanistic insight, protocol standardization, and regulatory clarity—the field is advancing rapidly. The convergence of cell therapy, PRP, EVs, and device-based modalities is creating a multifaceted toolkit for urologic regeneration. With continued scientific rigor, large-scale clinical trials, and interdisciplinary collaboration, regenerative medicine holds the potential to shift urologic care from chronic symptomatic management to durable, tissue-level cure.Stem Cell Therapy: Advancements and Clinical Insights for Erectile Dysfunction Treatment Erectile dysfunction (ED)—defined as the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual activity—affects over 150 million men worldwide. While phosphodiesterase-5 inhibitors (PDE5is) remain the first-line treatment, many patients, particularly those with diabetes, age-related vascular decline, or neuropathy following radical prostatectomy, show suboptimal responses. Consequently, regenerative medicine—particularly stem-cell therapy—has gained interest for its potential to address the root causes of ED rather than merely managing symptoms.
Stem-cell therapy offers a multifaceted approach to treating ED through neuroregeneration, angiogenesis, anti-apoptotic signaling, and fibrosis inhibition. Once introduced into the target tissue, stem cells can differentiate into specific cell types or exert paracrine effects via secretion of growth factors and extracellular vesicles. Among the various sources studied, bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived stem cells (ADSCs), and umbilical cord-derived MSCs (UC-MSCs) have been most extensively explored.
Preclinical studies consistently demonstrate that MSC-based therapies enhance cavernous nerve regeneration, suppress fibrosis, and preserve endothelial integrity. In rat models of diabetes- or nerve-injury-induced ED, intracavernosal injections of ADSCs or BM-MSCs significantly restore intracavernosal pressure (ICP) and improve corpus cavernosum histology. Phase I/II clinical trials also support the safety and preliminary efficacy of stem-cell approaches. For example, in men with diabetic ED treated with autologous BM-MSCs, significant improvements in International Index of Erectile Function-5 (IIEF-5) scores and penile arterial flow have been reported without major adverse events. Similarly, ADSC therapy in post-prostatectomy ED has shown encouraging short-term results. However, large-scale trials are needed to clarify long-term efficacy, immune responses, and safety profiles.
Human amniotic fluid stem cells (hAFSCs) represent a promising alternative, offering characteristics that bridge embryonic and adult stem-cell profiles. These include broad multipotency, high proliferation, and low immunogenicity—traits ideal for allogeneic use and neuroregenerative purposes. Notably, hAFSCs secrete potent regenerative mediators such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), all of which support neurovascular repair and smooth muscle integrity. Our recent studies demonstrate, for the first time, that hAFSCs persist long-term in penile tissue and can differentiate into cavernous smooth-muscle cells, effectively replacing damaged tissue and improving erectile function even in chronic neurogenic ED models.
Despite these advantages, our findings did not reveal in-vivo homing of hAFSCs to nerve injury sites or differentiation into neural tissue. This suggests a need for future studies to identify the specific microenvironmental cues required to induce such responses. Additionally, combining hAFSCs with platelet-rich plasma (PRP) may provide synergistic benefits—enhancing stem-cell homing, paracrine signaling, and in-vivo differentiation—thereby advancing a more effective, scalable, and safe therapeutic strategy.
Hidenori AkaihataJapanSpeakerThe Activation of Humoral Immunity Causes Lower Urinary Tract Dysfunction Related with Prostate Through the Different Mechanism from the Prostate VolumeAim of this study
The prostate volume and morphological features of the prostate are well known to be associated with lower urinary tract dysfunction (LUTD) in the male patients. However, the causative agents and factors of LUTD related with prostate are multifactorial and incompletely understood. The aim of this study was to find out the novel mechanism underlying LUTD related with prostate except for prostate volume and morphological features.
Materials and methods
A total of 31 patients who had a diagnosis of benign by the random prostate biopsy were enrolled in this study. Comprehensive gene expression analysis (CGEA) was performed with prostate specimens obtained by the prostate biopsy. The patients were divided into control group (prostate volume < 30 mL) and benign prostatic enlargement (BPE) group (prostate volume ≥ 30 mL). Hierarchical clustering was performed to identify the clusters with similar gene expression by the genes indicated significantly different between two groups by t-test. The histological examinations and uroflowmetry parameters were compared among each cluster by Mann-Whitney's U test.
Results
CGEA selected 12 genes with significant difference in mean converted value between control and BPE (P<0.01) from 11,907 genes. Hierarchical clustering analysis using these 12 genes categorized three different clusters: the control (n=8), the BPE (n=11) and BPE with inflammatory (n=12) clusters. As compared BPE cluster, the BPE with inflammatory cluster have activation of humoral immunity (increased VSIG2 gene and reduced MME gene). The collagen/muscle was significantly increased in the BPE with humoral immunity cluster as compared with other clusters (control vs BPE with inflammatory P=0.04, BPE vs BPE with inflammatory P<0.01). The maximum flow rate was significantly lower in the BPE with inflammatory cluster than in the control cluster (P=0.03). There was no significant difference about the maximum flow rate between control cluster and BPE cluster.
Conclusions
Our results suggested that inflammation by activated humoral immunity in the prostate cause prostatic fibrosis, resulting in the LUTD through the increased urethral resistance.