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

Jhang, Jia‐Fong; Jiang, Yuan‐Hong; Hsu, Yuan-Hsiang; Ho, Han‐Chen; Birder, Lori A.; Lin, Teng-Yi; Kuo, Hann‐Chorng

doi:10.5213/inj.2142100.050

Cited by 13 publications

(16 citation statements)

References 23 publications

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“…Expressions of urothelium Shh, CK5, ZO-1, E-cadherin, and transforming growth factor β also 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 a GRA ≥ 1 or improved VAS but not in patients with a GRA of 0 and no improvement in VAS [ 73 ]. Besides the IC symptom scores, we could investigate the therapeutic efficacy of treatment for IC/BPS patients using the urothelial barrier markers, cytoskeletal maturation markers, and progenital cell markers ( Figure 3 ).…”

Section: Improvement Of Urothelial Regeneration In Ic/bps Bladders Af...mentioning

confidence: 99%

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment

2022

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Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

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Section: Improvement Of Urothelial Regeneration In Ic/bps Bladders Af...mentioning

confidence: 99%

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment

2022

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“…Immunohistochemistry study showed that four repeated PRP injections increased the expression of the urothelial cell proliferation marker Sonic hedgehog protein and cytoskeleton marker CK 5 , as well as the expression of adhesive proteins E-cadherin and ZO-1, in patients with IC/BPS, indicating that PRP injections can increase progenitor cell proliferative activity and facilitate barrier protein expression. ( Jhang et al, 2022 ). However, not all urothelial proteins show similar changes after PRP injection.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy of Intravesical Platelet-Rich Plasma Injections for Interstitial Cystitis/Bladder Pain Syndrome—A Comparative Study of Different Injection Number, Additives and Concentrations

et al. 2022

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Purpose: Intravesical platelet-rich plasma (PRP) injections have been demonstrated effective in relieving symptoms among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This study compared the clinical efficacy among different injection number, adding solution, and concentrations of PRP.Methods: A total of 63 patients with IC/BPS were enrolled and randomly allocated to four subgroups who received single high-dose PRP (from 100 ml whole blood) plus 10 ml of normal saline or plasma injected over 20 or 40 sites. Patients were followed up at 1, 3, and 6 months for changes in the IC symptom index (ICSI) and problem index (ICPI), visual analog scale (VAS), global response assessment (GRA), and urodynamic parameters. Furthermore, we compared the clinical outcome with our previous study in a group of 55 IC/BPS patients who underwent four monthly low-dose PRP (from 50 ml whole blood) injections.Results: The result of this study showed significant improvements in IC symptoms (ICSI 11.9 ± 4.4 vs. 10.2 ± 4.9, p = 0.009; ICPI 12.3 ± 3.4 vs. 10.6 ± 4.7, p = 0.003); VAS (5.46 ± 2.96 vs. 3.83 ± 3.1, p 0.000), and maximum flow rate (10.4 ± 4.9 vs. 17.1 ± 11.5 ml/s, p = 0.000) at 3 months after single high-dose PRP injection. However, no significant differences in therapeutic results were observed among subgroups, regardless of the added component or injecting site. The improvements of ICSI, ICPI, and GRA at 6 months were lower in comparison with the results of four low-dose PRP injections. All patients were free of dysuria, urinary retention, or urinary tract infection after PRP treatment.Conclusion: Intravesical PRP injection is effective for IC/BPS. The addition of normal saline or plasma and injection site had no influence on therapeutic efficacy. However, the symptom improvement and GRA after a single high-dose PRP injection was lower than that after four low-dose PRP injections 6 months after the first treatment. Limitation of the study is lack of sham control group.

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“…After four PRP injections in patients with IC/BPS, urinary levels of NGF, MMP-13, and VEGF decreased, and PDGF-AB levels significantly increased in responders, suggesting that PRP injections decrease inflammation, resulting in improvements in bladder pain and frequency episodes [ 48 ]. In addition, the expression of the urothelial barrier function protein and the urothelial cell proliferation protein increased after repeated PRP injections [ 49 ]. Thus, intravesical PRP injections may improve urothelial regeneration and differentiation to recreate a healthy urothelial barrier in IC/BPS bladders [ 50 ].…”

Section: Treatment Targeting Urothelial Dysfunction and Regenerative ...mentioning

confidence: 99%

Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

2022

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The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. Patients with Hunner’s lesion (HIC) and without Hunner’s lesion (NHIC) should be treated differently. Based on the histopathological findings, NHIC can be treated with intravesical instillation of urothelial protective agents, such as hyaluronic acid, to cover the urothelial defects. In non-responders, chronic inflammation and higher urothelial dysfunction can be treated with intravesical botulinum toxin A injection, platelet-rich plasma injection, or low-energy shock wave treatment to reduce inflammation, increase tissue regeneration, and improve the urothelial barrier. Patients with HIC should be treated with electrocauterization first; augmentation enterocystoplasty should only be used in end-stage HIC when the contracted bladder is refractory to other treatments. The antiviral agent, valacyclovir, can be used in patients with HIC, small bladder capacity, and high-grade glomerulations. In addition, behavioral modification is always recommended from the beginning of treatment. Treatment with cognitive behavioral therapy interventions in combination with bladder therapy can reduce anxiety and improve treatment outcomes. Herein, recent advances in the pathophysiology and novel treatments for IC/BPS are reviewed.

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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

Cited by 13 publications

References 23 publications

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment

Therapeutic Efficacy of Intravesical Platelet-Rich Plasma Injections for Interstitial Cystitis/Bladder Pain Syndrome—A Comparative Study of Different Injection Number, Additives and Concentrations

Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

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