scholarly journals The study on the function and cell source of interleukin‐6 in interstitial cystitis/bladder painful syndrome rat model

Author(s):  
Zhenming Zheng ◽  
Jiapeng Zhang ◽  
Caixia Zhang ◽  
Wenshuang Li ◽  
Kaiqun Ma ◽  
...  
Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 86 ◽  
Author(s):  
Jung Hyun Shin ◽  
Chae-Min Ryu ◽  
Hyein Ju ◽  
Hwan Yeul Yu ◽  
Sujin Song ◽  
...  

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.


2011 ◽  
Vol 8 (7) ◽  
pp. 1957-1964 ◽  
Author(s):  
Shinichi Yamashita ◽  
Ryuichi Kato ◽  
Ko Kobayashi ◽  
Shin‐ichi Hisasue ◽  
Yoichi Arai ◽  
...  

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Daniele Porru ◽  
Valentina Bobbi ◽  
Carmelo Di Franco ◽  
Alessandra Viglio ◽  
Mattia Novario ◽  
...  

The aim was to find out whether a correlation exists between denudation of urothelium and time of symptom onset in patients with bladder pain syndrome/interstitial cystitis (BPS/IC), and to search a correlation between impact of symptoms evaluated with ICSI-ICPI and the presence of comorbid conditions associated with BPS/IC. Ninety-seven consecutive patients underwent cystoscopy under general anesthesia to classify those cases suspected of being affected from BPS/IC. Three cold bladder biopsies were taken including detrusor muscle. Statistical analysis showed significant correlation between IC/BPS duration and the presence of Hunner’s lesions (P<0.023). Hunner’s lesion with cystoscopy and histological evidence of urothelial denudation with bladder biopsy appear to be items related to IC/BPS duration. Thus an early diagnosis allows to start an appropriate therapeutic approach and prevent a more severe evolution of this multifaceted painful syndrome. Our study shows a correlation between time of symptom onset and evidence of urothelial denudation and with detrusor mast cell count in the whole group of patients. IC/BPS duration seem to correlate with the presence of associated diseases.


2019 ◽  
Vol 122 (3) ◽  
pp. 1136-1146 ◽  
Author(s):  
Nicolas Montalbetti ◽  
James G. Rooney ◽  
Anna C. Rued ◽  
Marcelo D. Carattino

The internal surface of the urinary bladder is covered by the urothelium, a stratified epithelium that forms an impermeable barrier to urinary solutes. Increased urothelial permeability is thought to contribute to symptom generation in several forms of cystitis by sensitizing bladder afferents. In this report we investigate the physiological mechanisms that mediate bladder afferent hyperexcitability in a rat model of cystitis induced by overexpression in the urothelium of claudin-2 (Cldn2), a tight junction-associated protein upregulated in bladder biopsies from patients with interstitial cystitis/bladder pain syndrome. Patch-clamp studies showed that overexpression of Cldn2 in the urothelium sensitizes a population of isolectin GS-IB4-negative [IB4(−)] bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials. Gene expression analysis revealed a significant increase in mRNA levels of the delayed-rectifier voltage-gated K+ channel (Kv)2.2 and the accessory subunit Kv9.1 in this population of bladder sensory neurons. Consistent with this finding, Kv2/Kv9.1 channel activity was greater in IB4(−) bladder sensory neurons from rats overexpressing Cldn2 in the urothelium than in control counterparts. Likewise, current density of TTX-S voltage-gated Na+ (Nav) channels was greater in sensitized neurons than in control counterparts. Significantly, guangxitoxin-1E (GxTX-1E), a selective blocker of Kv2 channels, blunted the repetitive firing of sensitized IB4(−) sensory neurons. In summary, our studies indicate that an increase in the activity of TTX-S Nav and Kv2/Kv9.1 channels mediates repetitive firing of sensitized bladder sensory neurons in rats with increased urothelial permeability. NEW & NOTEWORTHY Hyperexcitability of sensitized bladder sensory neurons in a rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) results from increased activity of tetrodotoxin-sensitive voltage-gated Na+ and delayed-rectifier voltage-gated K+ (Kv)2/Kv9.1 channels. Of major significance, our studies indicate that Kv2/Kv9.1 channels play a major role in symptom generation in this model of IC/BPS by maintaining the sustained firing of the sensitized bladder sensory neurons.


2015 ◽  
Vol 128 (7) ◽  
pp. 956-962 ◽  
Author(s):  
Ya-Qiang He ◽  
Wei-Tao Zhang ◽  
Chang-Hua Shi ◽  
Fang-Ming Wang ◽  
Xiao-Jun Tian ◽  
...  

2020 ◽  
Vol 12 ◽  
Author(s):  
Jiangnan Ma ◽  
Jinzhao Gao ◽  
Mengyue Niu ◽  
Xiaona Zhang ◽  
Jing Wang ◽  
...  

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