Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis

Yuan-Hong Jiang, Yuh-Chen Kuo, Jia-Fong Jhang, Cheng-Ling Lee, Yung-Hsiang Hsu, Han-Chen Ho, Hann-Chorng Kuo, Yuan-Hong Jiang, Yuh-Chen Kuo, Jia-Fong Jhang, Cheng-Ling Lee, Yung-Hsiang Hsu, Han-Chen Ho, Hann-Chorng Kuo

Abstract

Repeated intravesical injections of autologous platelet-rich plasma (PRP) have been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a paucity of objective evidence of the effectiveness of this therapy. In this study, we investigated the changes in urinary markers after PRP treatment. Forty patients with IC/BPS who were refractory to conventional therapy received four injections of PRP at monthly intervals; 10 mL PRP solution with 2.5 times the peripheral blood platelet concentration was used. Urine levels of thirteen functional proteins, growth factors, and cytokines were assessed at baseline and at the 4th PRP injection. The clinical parameters included visual analog scale (VAS) pain score, daily urinary frequency, nocturia episodes, functional bladder capacity, and global response assessment (GRA). The GRA and symptom score significantly decreased post-treatment. In patients with GRA ≥ 2, the success rates at 1 month and at 3 months after the 4th PRP injection were 70.6% and 76.7%, respectively. The VAS pain score, frequency, and nocturia showed a significant decrease (all p < 0.05). Urinary levels of nerve growth factor, matrix metalloproteinase-13, and vascular endothelial growth factor significantly decreased post-treatment (p = 0.043, p = 0.02, and p = 0.000, respectively); platelet-derived growth factor-AB showed a significant increase (p = 0.004) at the 4th PRP treatment compared with baseline. In this study, repeated intravesical PRP injections provided significant symptom improvement in IC/BPS patients with concomitant changes in the related biomarker levels.Trial registration: ClinicalTrial.gov: NCT03104361; IRB: TCGH 105-48-A.

Conflict of interest statement

The authors declare no competing interests.

References

    1. Keay S. Cell signaling in interstitial cystitis/painful bladder syndrome. Cell Signal. 2008;20:2174–2179. doi: 10.1016/j.cellsig.2008.06.004.
    1. Homma Y, et al. Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015. Int. J. Urol. 2016;23:542–549. doi: 10.1111/iju.13118.
    1. Shie JH, Kuo HC. 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. BJU Int. 2011;108:E136–141. doi: 10.1111/j.1464-410X.2010.09911.x.
    1. Lowe EM, et al. Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br. J. Urol. 1997;79:572–577. doi: 10.1046/j.1464-410X.1997.00097.x.
    1. Okragly AJ, et al. Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J. Urol. 1999;161:438–441. doi: 10.1016/S0022-5347(01)61915-3.
    1. Coelho A, et al. Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels. Br. J. Pharmacol. 2015;172:1691–1699. doi: 10.1111/bph.12958.
    1. Jiang YH, Liu HT, Kuo HC. Decrease of urinary nerve growth factor but not brain-derived neurotrophic factor in patients with interstitial cystitis/bladder pain syndrome treated with hyaluronic acid. PLoS ONE. 2014;10(9):91609. doi: 10.1371/journal.pone.0091609.
    1. Shie JH, Liu HT, Kuo HC. Increased cell apoptosis of the urothelium is mediated by inflammation in interstitial cystitis/painful bladder syndrome. Urology. 2012;79(484):e7–13.
    1. Arican O, Aral M, Sasmaz S, Ciragil P. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediat. Inflamm. 2005;2005:273–279. doi: 10.1155/MI.2005.273.
    1. Rath PC, Aggarwal BB. TNF-induced signaling in apoptosis. J. Clin. Immunol. 1999;19:350–364. doi: 10.1023/A:1020546615229.
    1. Jhang JF, et al. Electron microscopic characteristics of interstitial cystitis/bladder pain syndrome and their association with clinical condition. PLoS ONE. 2018;13:e0198816. doi: 10.1371/journal.pone.0198816.
    1. Tamaki M, Saito R, Ogawa O, Yoshimura N, Ueda T. Possible mechanisms inducing glomerulations in interstitial cystitis: relationship between endoscopic findings and expression of angiogenic growth factors. J. Urol. 2004;172:945–948. doi: 10.1097/01.ju.0000135009.55905.cb.
    1. Furuta A, et al. Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with IC/BPS. Int. J. Urol. 2019;26(Suppl 1):35–40. doi: 10.1111/iju.13972.
    1. Kiuchi H, et al. Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations. BJU Int. 2009;104:826–831. doi: 10.1111/j.1464-410X.2009.08467.x.
    1. Wang J, et al. Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-beta1. Am. J. Physiol. Renal Physiol. 2017;313:F961–F972. doi: 10.1152/ajprenal.00686.2016.
    1. Jhang JF, Wang HJ, Hsu YH, Birder LA, Kuo HC. Upregulation of neurotrophins and transforming growth factor-β expression in the bladder may lead to nerve hyperplasia and fibrosis in patients with severe ketamine-associated cystitis. Neurourol. Urodyn. 2019;38:2303–2310. doi: 10.1002/nau.24139.
    1. Cai G, et al. Tissue inhibitor of metalloproteinase-1 exacerbated renal interstitial fibrosis through enhancing inflammation. Nephrol. Dial. Transplant. 2008;23:1861–1875. doi: 10.1093/ndt/gfm666.
    1. Etulain J. Platelets in wound healing and regenerative medicine. Platelets. 2018;14:1–13.
    1. Mussano F, et al. Cytokine, chemokine, and growth factor profile of platelet-rich plasma. Platelets. 2016;27:467–471. doi: 10.3109/09537104.2016.1143922.
    1. Jhang JF, Wu SY, Lin TY, Kuo HC. Repeated intravesical injections of platelet-rich plasma are effective in the treatment of interstitial cystitis: a case control pilot study. Low. Urin. Tract Symptoms. 2019;11:O42–O47. doi: 10.1111/luts.12212.
    1. Jhang JF, Lin TY, Kuo HC. Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-a prospective clinical trial. Neurourol. Urodyn. 2019;38:703–709. doi: 10.1002/nau.23898.
    1. Nazif O, Teichman JM, Gebhart GF. Neural upregulation in interstitial cystitis. Urology. 2007;69(Suppl):24–33. doi: 10.1016/j.urology.2006.08.1108.
    1. Homma Y, et al. Clinical guidelines for interstitial cystitis and hypersensitive bladder syndrome. Int. J. Urol. 2009;16:597–615. doi: 10.1111/j.1442-2042.2009.02326.x.
    1. Shie JH, Liu HT, Kuo HC. Protein expression profiling in interstitial cystitis/painful bladder syndrome: a pilot study of proteins associated with inflammation, apoptosis and angiogenesis. Urol. Sci. 2012;23:107–113. doi: 10.1016/j.urols.2012.10.003.
    1. Parsons CL. The potassium sensitivity test: a new gold standard for diagnosing and understanding the pathophysiology of interstitial cystitis. J. Urol. 2009;182:432–434.
    1. Saban R. Angiogenic factors, bladder neuroplasticity and interstitial cystitis-new pathobiological insights. Transl. Androl. Urol. 2015;4:555–562.
    1. Peng CH, Jhang JF, Shie JH, Kuo HC. Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical OnabotulinumtoxinA injections combined with hydrodistention for patients with interstitial cystitis–clinical results and immunohistochemistry analysis. Urology. 2013;82(1452):e1–6.
    1. Lai HH, et al. Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study. BJU Int. 2017;120:576–583. doi: 10.1111/bju.13924.
    1. Hannink M, Donoghue DJ. Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim. Biophys. Acta. 1989;989:1–10.
    1. Peters KM, et al. Effect of sacral neuromodulation on outcome measures and urine chemokines in interstitial cystitis/painful bladder syndrome patients. Low. Urin. Tract Symptoms. 2015;7:77–83. doi: 10.1111/luts.12054.
    1. Amable PR, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res. Ther. 2013;4:67. doi: 10.1186/scrt218.
    1. Etulain J, et al. An optimised protocol for platelet-rich plasma preparation to improve its angiogenic and regenerative properties. Sci. Rep. 2018;8:1513. doi: 10.1038/s41598-018-19419-6.
    1. Propert KJ, Interstitial Cystitis Clinical Trials Group Responsiveness of symptom scales for interstitial cystitis. Urology. 2006;67:55–59. doi: 10.1016/j.urology.2005.07.014.

Source: PubMed

3
Předplatit