Hypothesis / aims of study
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic syndrome characterized by chronic pelvic pain (> 6 months) with lower urinary tract symptoms. Due to the lack of a clear understanding of the etiology, there is no consensus regarding the optimal treatment approach for IC/BPS. It is known that there are various growth factors enriched in platelet rich plasma (PRP). Autologous platelet-rich plasma (PRP) is growing in popularity as a therapy to augment wound healing and to speed up the recovery injuries. Our previous pilot study reported repeated intravesical PRP improved symptoms in IC/BPS.The aim of our study is to investigate the effects of repeated intravesical PRP injections in enhancing epidermal protection and reducing chronic inflammations of the bladder among patients who suffered from refractory IC/BPS.
Study design, materials and methods
The IC/BPS patients who were treated at our hospital were enrolled into this study. All patients had been initially treated at least two therapy conservatively but failed. All of the patients had completed four monthly intravesical injections of 10 mL PRP extracted from 50 mL of whole blood. Urine samples were collected for measuring urinary vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BNDF), nerve growth factor (NGF), transforming growth factor beta 1(TGF-β1), platelet-derived growth factor (PDGF)-AA, PDGF-AB, matrix metalloproteinase (MMP), and cytokines including interleukin IL-2, IL-6 and IL-8, IL-1β, TNFα levels at baseline and 12 weeks after first injection. The clinical symptoms, urodynamic study, urine cytokines, functional proteins and growth factors before and after PRP injections were recorded. We compared the difference between each time of PRP injections, one month and three month later after finished therapy. The assessment indicator were evaluated by the global response assessment (GRA) at one months after the 3rd PRP injection , which were divided patients into two groups according to the change of GRA (∆GRA ≥ 2 or <2). We compared the difference between the two groups to investigate the factor of treatment outcome.
Results
A total of 40 IC/BPS patients (37 female; 3 Male, aged 55.5 ± 11.1 years) were enrolled. The improvements in clinical symptom (frequency, nocturia and VAS), symptom scores (ICSI, ICPI, GRA and OSS), UDS parameters (Qmax and volume) and high GRA changed (success rate was 45%, 52%, 70%, 70%, and 67.5% after the 1st, 2nd, 3rd, 4th, and 3 months after the 4th PRP injection) were recorded in our previous study [1]. The results of this study revealed that patients undergoing repeated PRP injection had some changes in urine cytokines, functional proteins and growth factors (nerve growth factor, Platelet-derived growth factor-AB, Matrix Metallopeptidase-13 and vascular endothelial growth factor) after full course of treatment (Table 1). After divided patients into two groups according to the ∆GRA, the changed of proteins including Matrix Metallopeptidase-13 and vascular endothelial growth factor in whole patients; Platelet-derived growth factor-AB, and nerve growth factor in clinical responder (∆GRA ≥ 2) group; and Interleukin-6 in clinical poor responder (GRA<2) group (Table 2). The Matrix Metallopeptidase-13 revealed difference of parameters at post-treatment between groups and the Interleukin-2 showed difference of parameters at baseline between groups (Table 2).
Interpretation of results
The study for the first time demonstrated that repeated intravesical injections of autologous PRP can provide IC symptom improvement in patients with IC/BPS refractory to conventional therapy. The urinary protein analysis also revealed that some inflammatory related proteins can be reduced after PRP injections, suggesting PRP injections into the IC bladder wall effectively decreased inflammation, which was also related to the improvement of bladder pain and frequency episodes. Autologous PRP injection is safe and effective in selected patients. The changes of these urinary proteins after intravesical PRP injections provide evidence that PRP can decrease inflammation, improve abnormal angiogenesis, and possibly increase the regeneration of the defective urothelium in IC/BPS bladder mucosa. In this study, we also noted the urinary marker levels except VEGF were not significantly higher those in the controls, we believe that is because all patients have been treated with various modalities previously but the IC symptoms still exist. Urinary marker levels might not reflect the true inflammatory condition in the bladder. Nevertheless, the significant changes of these urinary markers after PRP treatment are associated with decrease of bladder pain, decrease of frequency, decrease of IC symptom indexes, and increase of GRA. Together with the negative KCl test after treatment, PRP injection might resume a homeostasis from the aberrant urothelial dysfunction. Although the effective therapeutic duration deserves further evaluation, this treatment provides a safe therapeutic alternative for the IC/BPS refractory to conventional therapies.
Concluding message
The study for the first time demonstrated that repeated intravesical injections of autologous PRP can provide IC symptom improvement in patients with IC/BPS refractory to conventional therapy. Urinary NGF, MMP-13, VEGF, levels decreased, and PDGF-AB increased significantly after repeated PRP injections, especially in patients with a successful treatment outcome. These urinary protein analyses also revealed that some inflammatory related proteins can be reduced after PRP injections, suggesting PRP injections into the IC bladder wall effectively decreased inflammation, which was also related to the improvement of bladder pain and frequency episodes. Autologous PRP injection is safe and effective in selected patients.