Improved Urothelial Cell Proliferation, Cytoskeleton and Barrier Function Protein Expression in the Patients With Interstitial Cystitis/Bladder Pain Syndrome After Intravesical Platelet-Rich Plasma Injection

Purpose To investigate urothelial cell proliferation, cytoskeleton, inflammation, and barrier function protein expressions in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) after intravesical platelet-rich plasma (PRP) injections Methods A total of 19 patients with IC/BPS underwent 4 monthly intravesical PRP injections. Bladder biopsies were taken at the first and fourth PRP treatment. The bladder specimens were analyzed using the Western blot and immunochemical staining for progenitor cell markers for sonic hedgehog (Shh), CD34, and cytoskeleton proteins cytokeratin 5 (CK5), CK14, CK20; barrier function markers for zonula occludens-1 (ZO-1), E-cadherin, and intercellular adhesive molecule-1, tryptase and transforming growth factor-β (TGF-β). Global response assessment (GRA) was used to evaluate treatment outcomes. Results The mean age of patients was 55.6 years. After PRP injections, the functional bladder capacity and maximum flow rate increased, and the visual analogue scale (VAS) of pain, interstitial cystitis (IC) symptom index, IC problem index, O’Leary-Sant symptom score, and GRA improved in all patients. Urothelium Shh, CK5, ZO-1, E-cadherin, and TGF-β expressions increased significantly after repeated PRP injections. By subgrouping, according to PRP treatment outcomes, significant increases in Shh, E-cadherin, and ZO-1 expressions were noted only in patients with GRA ≥1 or improved VAS, but not in patients with GRA=0 and no improvement in VAS. Conclusions The level of urothelial barrier function protein and cell proliferation protein expression in the patients with IC/BPS was increased after repeat intravesical PRP injections. Intravesical repeat PRP injections may have potential to improve urothelial health and result in symptoms improvement in the patients with IC/BPS.

[1]  Y. Hsu,et al.  Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis , 2020, Scientific Reports.

[2]  H. Kuo,et al.  Intravesical injections of platelet‐rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment—A prospective clinical trial , 2019, Neurourology and urodynamics.

[3]  Han-Chen Ho,et al.  Electron microscopic characteristics of interstitial cystitis/bladder pain syndrome and their association with clinical condition , 2018, PloS one.

[4]  S. Egawa,et al.  Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity, and nociception in a chemically induced interstitial cystitis-like rat model , 2018, International Urogynecology Journal.

[5]  J. Etulain.  Platelets in wound healing and regenerative medicine , 2018, Platelets.

[6]  A. Kanai,et al.  Urothelial proliferation and regeneration after spinal cord injury. , 2017, American journal of physiology. Renal physiology.

[7]  Shiying Li,et al.  The Regulatory Effects of Transforming Growth Factor-β on Nerve Regeneration , 2017, Cell transplantation.

[8]  S. Petrillo,et al.  Cytokine, chemokine, and growth factor profile of platelet-rich plasma , 2016, Platelets.

[9]  D. Kuffler.  Platelet-Rich Plasma and the Elimination of Neuropathic Pain , 2013, Molecular Neurobiology.

[10]  Fei-Chi Chuang,et al.  Increased Urothelial Cell Apoptosis and Chronic Inflammation Are Associated with Recurrent Urinary Tract Infection in Women , 2013, PloS one.

[11]  Yan Geng,et al.  p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia , 2013, Proceedings of the National Academy of Sciences.

[12]  H. Kuo,et al.  Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. , 2012, Urology.

[13]  H. Kuo,et al.  Higher levels of cell apoptosis and abnormal E‐cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome , 2011, BJU international.

[14]  P. Beachy,et al.  Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder , 2011, Nature.

[15]  S. Keay.  Cell signaling in interstitial cystitis/painful bladder syndrome. , 2008, Cellular signalling.

[16]  P. Hauser,et al.  Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis. , 2008, The Journal of urology.

[17]  F. Smedts,et al.  Keratin expression profiling of transitional epithelium in the painful bladder syndrome/interstitial cystitis. , 2006, American journal of clinical pathology.

[18]  G. Sant,et al.  Responsiveness of symptom scales for interstitial cystitis. , 2006, Urology.

[19]  M. Kreft,et al.  Urothelial injuries and the early wound healing response: tight junctions and urothelial cytodifferentiation , 2005, Histochemistry and Cell Biology.

[20]  R. Hurst,et al.  Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis. , 2004, The Journal of urology.

[21]  C. Brensinger,et al.  Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. , 2001, Urology.