Molecular Mechanisms and Key Processes in Interstitial, Hemorrhagic and Radiation Cystitis.
Biology
Cystitis is a bladder disease with a high rate of prevalence in the world population. This report focuses on Interstitial Cystitis (IC), Hemorrhagic Cystitis (HC) and Chronic Radiation Cystitis. These pathologies have different etiologies, but they share common symptoms, for instance, pain, bleeding, and a contracted bladder. Overall, treatments are quite similar for abacterial cystitis, and include bladder epithelium protective or anti-inflammatory agents, alleviating pain and reducing bleeding. This review summarizes the mechanisms that the pathologies have in common, for instance, bladder dysfunction and inflammation. Conversely, some mechanisms have been described as present in only one pathology, such as neural regulation. Based on these specificities, we propose identifying a mechanism that could be common to all the above-mentioned pathologies.
10.3390/biology11070972
Interstitial Cystitis Can Be Improved With Intravesical Instillation of Platelet-Rich Plasma.
Hardy Timothy J
Cureus
Intravesical instillation of platelet-rich plasma has the potential to improve symptoms and reduce pain in patients who have interstitial cystitis and painful bladder syndrome by utilizing the body's own growth factors found in platelets. Interstitial cystitis is a disease of the bladder that causes pain, urinary frequency, urgency, and nocturia. It is difficult to treat and has unknown etiology. Patients who have interstitial cystitis have high rates of anxiety as a comorbid condition. People with anxiety are known to have dysregulation of serotonin. These concepts are interrelated.
10.7759/cureus.22747
The Early Histological Effects of Intravesical Instillation of Platelet-Rich Plasma in Cystitis Models.
Dönmez M İrfan,İnci Kubilay,Zeybek Naciye Dilara,Doğan H Serkan,Ergen Ali
International neurourology journal
PURPOSE:To evaluate the early histological effects of the intravesical instillation of platelet-rich plasma (PRP) in rabbit models of interstitial and hemorrhagic cystitis. METHODS:Thirty-six rabbits were classified into 6 groups: saline (S), S+PRP, hydrochloric acid (HCl), HCl+PRP, cyclophosphamide (CyP), and CyP+PRP. At 48 hours after induction, PRP was prepared and intravesically administered to the S+PRP, HCl+PRP, and CyP+PRP groups. Bladder sections were stained with toluidine blue for mast cell counting and with hematoxylin and eosin for histopathology and mitotic index determination. The proliferation index was determined by proliferating cell nuclear antigen (PCNA) immunolabeling. The nonparametric Mann-Whitney U-test was used for statistical analysis. RESULTS:No abnormalities were observed in the S group, whereas increased interstitial edema and increased average mitotic and proliferation indices were observed in the S+PRP group (P=0.023, P=0.004, and P=0.009, respectively). Intense epithelial loss, hemorrhage, and leukocyte infiltration were detected in the HCl and HCl+PRP groups, whereas a significantly increased average mitotic index was observed in the HCl+PRP group (P=0.002). When compared with its CyP counterpart, a significant reduction in hemorrhage and an increase in leukocyte infiltration and mitotic index were observed in the CyP+PRP group (P=0.006, P=0.038, and P=0.002, respectively). In addition, PCNA staining revealed a significantly increased proliferation index in the HCl+PRP and CyP+PRP groups (P=0.032 and P=0.015, respectively). CONCLUSIONS:The intravesical instillation of PRP increased the mitotic index in the saline and cyclophosphamide groups while decreasing macroscopic bleeding.
10.5213/inj.1632548.274
Protective Effect of Intravesical Platelet-Rich Plasma on Cyclophosphamide-Induced Hemorrhagic Cystitis.
Ozyuvali E,Yildirim M E,Yaman T,Kosem B,Atli O,Cimentepe E
Clinical and investigative medicine. Medecine clinique et experimentale
PURPOSE:Hemorrhagic cystitis (HC) is the most common urotoxic side effect of cyclophosphamide (CYP). Platelet rich plasma (PRP) plays an important role in wound healing and inflammatory responses. The aim of this study was to investigate the efficacy of intravesical PRP at treatment of interstitial cystitis (IC). MATERIAL-METHODS:Female rats (n=24) were used. IC was induced by intraperitoneal injection of cyclophosphamide (CYP). Rats were randomly allocated to one of four groups (n = 6 per group): a control group; a sham group with saline (75 mg/kg; i.p.) instead of CYP on day 1; a IC group, which was injected with CYP (150 mg/kg; i.p.) on day 1; and, a intravesical PRP‑treated group which was injected with CYP (150 mg/kg; i.p.) on day 1. On day 2, the rats in each group were sacrificed under anesthesia. RESULTS:Histological evaluation showed that bladder inflammation in CYP‑treated rats was not suppressed by PRP. CYP administration induced severe IC with marked edema, hemorrhage and inflammation in CYP and CYP+PRP groups, but PRP was not found to be effective to decrease these effects. CONCLUSION:The application of PRP could not reverse the histopathological changes in rats that had interstitial cystitis due to the cyclophosphamide injection.
Repeated intravesical injections of platelet-rich plasma are effective in the treatment of interstitial cystitis: a case control pilot study.
Jhang Jia-Fong,Wu Shu-Yu,Lin Teng-Yi,Kuo Hann-Chorng
Lower urinary tract symptoms
OBJECTIVE:Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a debilitating chronic disease. There are few treatment options for IC/BPS refractory to current medical therapy. This study investigated the clinical efficacy of intravesical injections of platelet-rich plasma (PRP) in IC/BPS. METHODS:Fifteen patients with IC/BPS received 4 intravesical injections, at 1-monthly intervals, of 12 mL PRP extracted from 50 mL of the patient's whole blood, followed by cystoscopic hydrodistention. The primary endpoint was the change in O'Leary-Sant symptom (OSS) index from baseline to 1 month after the 4th PRP injection. Secondary endpoints were changes in pain (measured using a visual analog scale [VAS]), daily frequency, nocturia, functional bladder capacity (FBC), maximum flow rate, voided volume, post-void residual (PVR) volume, and global response assessment (GRA). Urinary cytokine levels were measured at baseline and 1 month after the 1st PRP treatment. RESULTS:Of the 15 women in the study, 13 completed the 4 injections and follow-up visits (mean [± SD] age 52.9 ± 12.1 years). The OSS index and VAS pain score decreased significantly and FBC and GRA increased after the 1st PRP injection and lasted until the final endpoint. There was no change in PVR after repeated PRP injections, and all patients were free of urinary tract infections and difficulty urinating. Urinary interleukin (IL)-2 and IL-8 concentrations increased significantly after the 1st PRP injection. In patients with reductions in the VAS pain score ≥1, urinary IL-8 and vascular endothelial growth factor increased. In patients without reductions in the VAS pain score, IL-6 concentrations increased after PRP injection. CONCLUSIONS:Repeated intravesical PRP injections are well tolerated and appear to be safe and effective in medically refractive IC/BPS, providing significant symptom improvement.
10.1111/luts.12212
Promising impact of platelet rich plasma and carbon dioxide laser for stress urinary incontinence.
European journal of obstetrics & gynecology and reproductive biology: X
OBJECTIVES:To evaluate the safety, feasibility and efficacy of trans-vaginal fractional micro-ablative CO laser therapy in combination with platelet rich plasma (PRP) for the treatment of stress urinary incontinence (SUI) in women. STUDY DESIGN:Participants with SUI underwent three sessions of transvaginal CO laser and PRP treatment, administered at 4-6-week intervals. Outcomes were assessed using the bladder function section of the Australian Pelvic Floor Questionnaire (APFQ). The primary outcome was changes in the participants' symptoms of SUI. Secondary outcomes were related to general bladder function. Outcome differences from baseline (T1) to 3 months (T2) and 12 months (T3) were analysed using Wilcoxon signed-rank tests. Subjective verbal scales were used to assess the degree of pain associated with PRP injections and laser treatment. RESULTS:Sixty-two women with SUI were enrolled into this study. There were 66% (41/62) of participants who reported improved SUI symptoms from T1 to T2 (p < 0.001) and at T3, 62% (23/37) of patients reported improved SUI symptoms (p < 0.001). From T1 to T2, all bladder function variables were improved significantly (p < 0.002). At T3, significant improvements (p < 0.03) were maintained for all bladder function variables, except pad usage (p = 0.073). CONCLUSIONS:Combining transvaginal fractional CO laser with PRP might be a beneficial treatment for SUI. It may have the potential to be a minimally-invasive and low-risk alternative to surgery, with reduced recovery time.
10.1016/j.eurox.2019.100099
Intravesical application of platelet-rich plasma in patients with persistent haemorrhagic cystitis after hematopoietic stem cell transplantation: a single-centre preliminary experience.
Masieri Lorenzo,Sessa Francesco,Mari Andrea,Campi Riccardo,Cito Gianmartin,Verrienti Pierangelo,Nozzoli Chiara,Saccardi Riccardo,Sforza Simone,Di Maida Fabrizio,Grosso Antonio Andrea,Carini Marco,Minervini Andrea
International urology and nephrology
PURPOSE:Haemorrhagic cystitis (HC) after allogeneic transplantation (HSCT) is a condition characterized by diffuse inflammation and bleeding from the bladder mucosa. Treatment of HC is not standardized and clinical Guidelines are elusive. The aim of this study was to evaluate the safety and efficacy of intravesical treatment with platelet-rich plasma (PRP) in patients with HC after allogenic HSCT. METHODS:Data from ten consecutive patients with BK virus-induced HC between 2013 and 2017 were collected. HC was classified into four grades. Inclusion criteria were (a) grade 3 or 4 BKV-induced HC after allogenic HSCT; (b) HC refractory to conservative therapy. All patients underwent transurethral cystoscopy and PRP treatment under general anaesthesia. RESULTS:Mean patients' age was 33.6 years. Four patients (40%) presented a grade 3 BKV-induced HC and six patients (60%) a grade 4. No intraoperative complications occurred. Postoperative complications were recorded in six patients: three patients required blood transfusion while three patients endovenous antibiotic therapy. Median time to catheter removal was 6 days (IQR 2-10). Median length of hospitalization was 35 days (IQR 6-73). At 30 days after surgery, a three-way catheter was repositioned in one patient for grade 4 haematuria, six patients had a complete response, and three a partial response. CONCLUSIONS:Our preliminary experience suggests that intravesical administration of PRP should be considered as a feasible and safe option for the treatment of BK-induced HC after HSCT. Future studies are needed to assess its potential value in other forms of haemorrhagic cystitis.
10.1007/s11255-019-02223-0
What is the potential use of platelet-rich-plasma (PRP) in cancer treatment? A mini review.
Heliyon
Platelet-rich-plasma (PRP) is an autologous human platelet concentrate extracted from plasma. PRP has been investigated in order to be used in many fields, with emphasis on the musculoskeletal field applied to sports injuries, as well as on other medical fields such as cardiac surgery, gynecology, pediatric surgery, urology, ophthalmology and plastic surgery. Cancer treatment is another important field where PRP should be investigated; thus, it is important validating PRP preparation protocols to be used in clinical research. Many protocols should be revised since, overall, most studies do not provide necessary information to allow them to be multiplied or replicated. The current review focuses on several topics about cancer, mainly on innovative studies about PRP use as a feasible therapeutic alternative to treat bladder cancer - a field where it could play a key role. Relevant aspects such as platelets' contribution to immune regulation and the supportive role they play in innate and adaptive immune functions are also addressed. Another important topic reviewed in the current study refers to inflammatory process regulation associated with cancer and thrombosis sites, which indicated that tumor-induced platelet activation could be used as an important therapeutic target in the future. New aspects concerning nitric oxide's ability to restrain platelet adhesion and aggregation in order to slow metastasis progress in cancer patients provide an important advantage in cancer treatment. Finally, the current review has pointed out perspectives and the main concerns about, and possibilities of, PRP use in cancer treatment.
10.1016/j.heliyon.2020.e03660
Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model.
Chen Yung-Hsiang,Man Kee-Ming,Chen Wen-Chi,Liu Po-Len,Tsai Kao-Sung,Tsai Ming-Yen,Wu Yu-Tzu,Chen Huey-Yi
Diagnostics (Basel, Switzerland)
BACKGROUND:Interstitial cystitis/painful bladder syndrome (IC/PBS) could be treated to ameliorate urothelial injury. Here, we investigated the efficacy of intravesical instillation with platelet-rich plasma (PRP) and hyaluronic acid for acute IC/PBS. METHODS:The effects of PRP and hyaluronic acid on the proliferation of normal human fibroblast cells (HFCs) were assessed. Additionally, thirty virgin female rats were randomized into five groups: group 1, saline-injected control; group 2, cyclophosphamide (CYP) plus intravesical instillation with normal saline; group 3, CYP plus intravesical instillation with hyaluronic acid (1 mg/mL); group 4, CYP plus intravesical instillation with PRP; and group 5, CYP plus intravesical instillation with PRP plus hyaluronic acid. A cystometry and histological assessments were performed. The expression of cell junction-associated protein zonula occludens-2 (ZO-2) and inflammatory cytokine interleukin 6 (IL-6) was also measured. RESULTS:Low dose PRP increased proliferation in HFCs. The acute IC/PBS rats showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus intravesical instillation with PRP group than in the CYP-induced acute IC/PBS group. Additionally, the expression of ZO-2 was increased and IL-6 was decreased in the CYP plus intravesical instillation with PRP group compared with the CYP-induced acute IC/PBS group. CONCLUSION:These findings suggest that PRP modulate urothelial repair, which ameliorate the increase in urination frequency in rats treated with CYP. Overall, PRP may confer potential benefits by acting as urothelial repair modulators.
10.3390/diagnostics10060381
New Frontiers or the Treatment of Interstitial Cystitis/Bladder Pain Syndrome - Focused on Stem Cells, Platelet-Rich Plasma, and Low-Energy Shock Wave.
Lin Chih-Chieh,Huang Yun-Ching,Lee Wei-Chia,Chuang Yao-Chi
International neurourology journal
Interstitial cystitis/bladder pain syndrome (IC/BPS), which is characterized by bladder pain and irritative voiding symptoms, is a frustrating disease without effective treatment. The cause is still largely not understood, although urothelium ischemia/hypoxia, apoptosis, denudation, and infiltration of inflammatory cells are common histopathological findings. The current uncertainty regarding the etiology and pathology of IC/BPS has a negative impact on its timely and successful treatment; therefore, the development of new treatment modalities is urgently needed. Herein, we present advances in our knowledge on this topic and review the potential application of regenerative medicine for the treatment of IC/BPS. This article provides information on the basic characteristics and clinical evidence of stem cells, platelet-rich plasma (PRP), and low-energy shock waves (LESWs) based on a literature review with a search strategy for articles related to IC/BPS, stem cells, PRP, and LESW published in MEDLINE and PubMed. Stem cells, PRP, and LESW, which modulate inflammatory processes and promote tissue repair, have been proven to improve bladder regeneration, relieve bladder pain, inhibit bladder inflammation, and increase bladder capacity in some preclinical studies. However, clinical studies are still in their infancy. Based on the mechanisms of action of stem cells, PRP, and LESW documented in many preclinical studies, the potential applications of regenerative medicine for the treatment of IC/BPS is an emerging frontier of interest. However, solid evidence from clinical studies remains to be obtained.
10.5213/inj.2040104.052
Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients.
Jandial Aditya,Mishra Kundan,Sandal Rajeev,Kant Sahu Kamal
Therapeutic advances in infectious disease
BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.
10.1177/2049936121991377
Urothelial health after platelet-rich plasma injection in intractable recurrent urinary tract infection: Improved cell proliferation, cytoskeleton, and barrier function protein expression.
Lower urinary tract symptoms
OBJECTIVE:This clinical study used autologous intravesical platelet-rich plasma (PRP) injections to treat patients with recurrent urinary tract infection (rUTI). Changes in urothelial proliferation, cytoskeleton, and barrier function protein expression after treatment were investigated. MATERIALS:All patients underwent 4-monthly intravesical PRP injections with 1-year follow-up. Successful treatment was defined as ≤2 UTI episodes within the preceding 1 year. Bladder biopsies were performed at the first and fourth PRP injection, and specimens were investigated by Western blot for the proteins sonic hedgehog (Shh), CD34, cytokeratin 5 (CK5), CK14, CK20, zonula occludens-1 (ZO-1), E-cadherin, inflammatory proteins tryptase and p38, apoptotic protein BAX (BCL2-associated X protein) and caspase-3, functional proteins M2 (muscarinic receptor 2) and M3, and beta-adrenoceptor-3, with glyceraldehyde phosphate dehydrogenase used as normalizing protein for quantification. RESULTS:The study enrolled 22 patients with rUTI and 17 controls, with successful outcome in 14 of 22 (63.6%) patients. Compared with controls, Western blot quantification results showed that rUTI patients had lower CD34, CK20, M3, and ZO-1, but higher CK5, BAX, and caspase-3 at baseline. The reduced CD34, CK20, M2, and M3 expressions at baseline were significantly increased after repeat PRP injections. Patients with a successful outcome had significant increase of CD34, Shh, CK20, M2, and M3 expressions after PRP injections. CONCLUSION:Intravesical PRP repeat injections improve the urothelial cell proliferation and increase the CK 20 expression in umbrella cells. PRP repeat injections have a beneficial effect on bladder urothelium-associated changes in rUTI. Thus, PRP injection may restore urothelial health and prevent UTI recurrence in intractable rUTI.
10.1111/luts.12364
Use of Intravesical Injections of Platelet-Rich Plasma for the Treatment of Bladder Pain Syndrome: A Comprehensive Literature Review.
Trama Francesco,Illiano Ester,Marchesi Alessandro,Brancorsini Stefano,Crocetto Felice,Pandolfo Savio Domenico,Zucchi Alessandro,Costantini Elisabetta
Antibiotics (Basel, Switzerland)
BACKGROUND:Bladder pain syndrome/interstitial cystitis (BPS/IC) or primary bladder pain syndrome (PBPS) is a complex and poorly understood condition. This comprehensive review aimed to discuss the potential application of platelet-rich plasma (PRP) in the treatment of BPS/IC. The pathophysiology of BPS/IC is characterized by urothelial damage that triggers a chain of events leading to chronic inflammation and other conditions. Frequently, in subjects affected by BPS/IC, recurrent urinary tract infection (rUTI) is associated with difficult therapeutic management. For these reasons, many oral and intravesical treatments (e.g., antibiotic therapy and intravesical anesthetic instillations) have been proposed to alleviate the symptoms of IC/BPS. However, the limitation of these treatments is the short duration of improvement. The purpose of this review is to analyze the efficacy of intravesical PRP injections in subjects with PBS/IC and to try to understand the potential therapeutic effects on the pathophysiology of this disease. METHODS:A nonsystematic literature search using Pubmed, EMBASE, Scopus, Web of Science, Medline was performed from January 2000 to August 2021. The following terms were combined to capture relevant publications: "platelet-rich plasma", "interstitial cystitis", "PRP", "bladder pain syndrome", and "painful bladder syndrome". RESULTS:After exclusion of non-pertinent studies/articles, we have analyzed 5 studies. In detail, 2 articles concerned preclinical studies in which animal models were used. The authors showed an improvement in the histological pattern with less bleeding in treated subjects, a lower presence of inflammatory cytokines and an increase in the mitotic index of urothelial cells in animals treated with intravesical PRP. In the three prospective clinical trials analyzed, patients with BPS/IC who underwent monthly intravesical PRP injections were found to have a statistically significant improvement in symptoms with modulation of growth factors and inflammatory proteins. CONCLUSIONS:New evidence suggests that treatment with intravesical PRP could improve urothelial regeneration and reduces chronic inflammation in BPS/IC, modifying the clinical history of its pathology.
10.3390/antibiotics10101194
Bladder Ultrastructure and Urinary Cytokine Abnormality in Patients with Recurrent Urinary Tract Infection and the Changes after Intravesical Platelet-Rich Plasma Injections.
Jhang Jia-Fong,Ho Han-Chen,Hsu Yuan-Hsiang,Jiang Yuan-Hong,Kuo Hann-Chorng
Biomedicines
This study investigates the bladder from patients with recurrent urinary tract infection (rUTI) at baseline and after intravesical platelet-rich plasma (PRP) injections. Patients with rUTI who underwent repeated intravesical PRP injections provided bladder and urine specimens at baseline and after treatment. Bladder specimens were investigated with electron microscopy and Western blotting. The urine sample was analyzed with commercially available Milliplex immunoassays. A total of 29 patients were enrolled. At baseline, the rUTI bladders exhibited defects of integrity in umbrella cells, a widened tight junction, and lysed organelles. Intracellular bacterial community incubations in the epithelial cells were also noted. Improvement in bladder defects after PRP injection was noted in 25-42% of patients. Bladder UPK3 expression was significantly lower in the patients with rUTI than in controls. Baseline levels of urinary inflammatory cytokine interleukin (IL)-6, IL-8, and brain-derived neurotrophic factor were higher in the patients with rUTI than in the controls, but there were lower levels of vascular endothelial growth factor and nerve growth factor. In the patients with rUTI who recovered from acute infection, the bladders still had immature urothelium, various ultrastructural defects, and elevated urinary inflammatory cytokines. PRP injection has the potential to promote bladder recovery in some of these patients.
10.3390/biomedicines10020245
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.
International neurourology journal
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. CONCLUSION: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.
10.5213/inj.2142100.050
Therapeutic Efficacy of Intravesical Platelet-Rich Plasma Injections for Interstitial Cystitis/Bladder Pain Syndrome-A Comparative Study of Different Injection Number, Additives and Concentrations.
Frontiers in pharmacology
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. 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. The result of this study showed significant improvements in IC symptoms (ICSI 11.9 ± 4.4 . 10.2 ± 4.9, = 0.009; ICPI 12.3 ± 3.4 . 10.6 ± 4.7, = 0.003); VAS (5.46 ± 2.96 . 3.83 ± 3.1, 0.000), and maximum flow rate (10.4 ± 4.9 . 17.1 ± 11.5 ml/s, = 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. 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.
10.3389/fphar.2022.853776
Changes in the Ultrastructure of the Bladder Urothelium in Patients with Interstitial Cystitis after Intravesical Injections of Platelet-Rich Plasma.
Biomedicines
Urothelial dysfunction is considered a key pathological mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS). Intravesical platelet-rich plasma (PRP) injections might be effective for treating IC/BPS. This prospective study investigated the changes in electron microscopic findings among IC/BPS patients after intravesical PRP injections. Twenty-six patients with refractory non-ulcer IC/BPS underwent monthly intravesical PRP injections for 4 months. Changes in clinical symptom scores and video urodynamic study parameters were assessed from baseline to after the PRP injections. A post-treatment Global Response Assessment (GRA) score ≥ 2 was considered a successful outcome. The mean GRA score was significantly higher after 4 PRP injections than at baseline. Approximately 42% of patients experienced successful outcomes after PRP treatment. Urothelial ultrastructural defects showed no significant differences between baseline and after the PRP injections. However, patients showed variable improvements in different urothelial defects (grade improvements: urothelium cell layers, 31%; umbrella cell integrity, 42%; umbrella cell surface uroplakin plaque, 54%; tight junctions between adjacent umbrella cells, 46%; lysed organelles, 58%; inflammatory cell infiltration, 31%). Patients with successful treatment outcomes showed significant improvements in urothelial tight junction defects. Repeated intravesical PRP injections are effective for improving IC/BPS symptoms as they promote urothelial ultrastructural defect recovery.
10.3390/biomedicines10051182
Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.
International journal of molecular sciences
The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason's trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.
10.3390/ijms23105771
Improved symptoms and signs of refractory interstitial cystitis in women after intravesical Nanofat plus platelet-rich plasma grafting: A pilot study.
Journal of the Chinese Medical Association : JCMA
Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder pain accompanied by irritative urinary symptoms, and typical cystoscopic and histological features. In this pilot study, we assessed the impact of lesion-targeted bladder injection therapy using a biocellular regenerative medicine on patients with refractory IC/BPS. The medicine, which was an autologous emulsified fat (Nanofat) and platelet-rich plasma (PRP) combination, was prepared intraoperatively. Six patients (aged 40-54 years), who completed a standard protocol of four consecutive treatments at 3-month intervals, were followed up at 6 months postoperatively. All patients (100%) reported marked (+3; +3 ~ -3) improvement of their overall bladder conditions. Mean bladder pain (from 8.2 to 1.7; range: 0 ~ 10), IC-related symptoms (from 18.5 to 5.7; range: 0 ~ 20), and bother (from 14.8 to 3.8; range: 0 ~ 16) improved significantly (p < 0.01). The normalization of bladder mucosal morphology with treatments was remarkable under cystoscopic examination, and no significant adverse events were found. The cultured mesenchymal stem cells from Nanofat samples of the six patients were verified in vitro. Our preliminary results suggest novel intravesical therapy with autologous Nanofat plus PRP grafting is safe and effective for refractory IC/BPS. Surgical efficacy might be attributed to an in vivo tissue engineering process.
10.1097/JCMA.0000000000000735
Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-A prospective clinical trial.
Jhang Jia-Fong,Lin Teng-Yi,Kuo Hann-Chorng
Neurourology and urodynamics
AIMS:Current treatments for interstitial cystitis/bladder pain syndrome (IC/BPS) are usually unsuccessful in achieving long-term bladder pain relief and irritable symptom improvement. This study investigated the clinical efficacy of platelet-rich plasma (PRP) intravesical injections on IC/BPS patients refractory to conventional therapies. METHODS:Forty patients received four monthly intravesical injections of 10 mL PRP extracted from 50 mL of whole blood. The primary end-point was Global Response Assessment (GRA) at 3 months after the 4th PRP injection. Secondary endpoints included changes in O'Leary-Sant symptom score (OSS), visual analog scale (VAS) of pain, daily frequency, nocturia, functional bladder capacity (FBC), maximum flow rate, voided volume, post-void residual volume (PVR) from baseline to 3 months after the 4th PRP injection. RESULTS:All 40 patients (37 women and 3 men, aged 55.5 ± 11.1 years) completed the four injections and follow-up visits. GRA improved after the 1st PRP injection and the satisfaction persists till the primary end-point. The success rate was 45%, 52%, 70%, 70%, and 67.5% after the 1st, 2nd, 3rd, 4th, and 3 months after the 4th PRP injection, respectively. OSS and VAS also significantly decreased. The PVR did not change after repeated PRP injections, FBC increased, frequency, and nocturia were decreased after PRP injections. All patients were free of urinary tract infection or difficulty urinating. CONCLUSION:The study demonstrated that repeated intravesical injections of autologous PRP can increase bladder capacity and provide IC symptom improvement in patients with IC/BPS refractory to conventional therapy. Autologous PRP injection is safe and effective in selected patients.
10.1002/nau.23898
Therapeutic potential of intravesical injections of platelet-rich plasma in the treatment of lower urinary tract disorders due to regenerative deficiency.
Ke Qian-Sheng,Jhang Jia-Fong,Lin Teng-Yi,Ho Han-Chen,Jiang Yuan-Hong,Hsu Yuan-Hsiang,Kuo Hann-Chorng
Ci ji yi xue za zhi = Tzu-chi medical journal
The bladder urothelium plays an important role of barrier function to prevent influx of urinary toxic substance and bacteria. When there is insult to the urinary bladder, the urothelium will start to regenerate on injury. However, several factors might affect the regenerative function of bladder urothelium, including aging, chronic inflammation, and system diseases such as diabetes and chronic kidney diseases (CKDs). Impairment of bladder mucosal regenerative function might result in defective urothelial cell differentiation as well as barrier function, which might be the underlying pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) and recurrent bacterial cystitis. Our previous immunohistochemistry (IHC) study and electron microscopic study revealed that the loss of normal umbrella cells and defective junction proteins in IC/BPS and recurrent cystitis. Platelet-rich plasma (PRP) has been previously used in many medical aspects as regenerative medicine therapy. PRP is rich in many growth factors and cytokines which modulate the process of inflammation and regeneration in the wound healing process. Recent pilot studies have shown that intravesical PRP injections improve IC symptoms and yield a success rate of 70% at 3 months after treatment. The results highly suggest that PRP injection could improve urothelial regenerative function and reduce chronic inflammation in IC patients. This article reviews recently published researches on the urothelial dysfunction biomarkers, urothelial cell differentiation, and urinary regenerative and inflammatory proteins in patients with IC/BPS or recurrent bacterial cystitis. The pathophysiology of the insufficient urothelial regeneration and differentiation; and chronic inflammation may induce urothelial dysfunction and further affect the regenerative ability of the diseased bladder urothelium in IC/BPS and recurrent bacterial cystitis are discussed.
10.4103/tcmj.tcmj_92_19
Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis.
Scientific reports
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.
10.1038/s41598-020-72292-0