MP28-04 THE EFFECT OF SELECTIVE α1A-ADRENOCEPTOR BLOCKER SILODOSIN ON URINARY BLADDER FUNCTION IN RAT MODEL OF CYCLOPHOSPHAMIDE INDUCED INTERSTITIAL CYSTITIS

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.

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Engineered Stem Cells Improve Neurogenic Bladder by Overexpressing SDF-1 in a Pelvic Nerve Injury Rat Model

Cell Transplantation ◽

10.1177/0963689720902466 ◽

2020 ◽

Vol 29 ◽

pp. 096368972090246 ◽

Cited By ~ 2

Author(s):

Guan Qun Zhu ◽

Seung Hwan Jeon ◽

Kyu Won Lee ◽

Hyuk Jin Cho ◽

U-Syn Ha ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Neurogenic Bladder ◽

Rat Model ◽

Bladder Wall ◽

Bladder Function ◽

Pelvic Nerve ◽

Injured Nerve

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1+) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1−). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1+, imMSCs/eSDF-1−, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1+ expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1+ improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1+ group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1+ group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1+ group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

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Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity and nociception in a chemically induced interstitial cystitis-like rat model

International Urogynecology Journal ◽

10.1007/s00192-018-3631-5 ◽

2018 ◽

Vol 30 (5) ◽

pp. 845-846

Author(s):

Dina El-Hamamsy

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Interstitial Cystitis ◽

Rat Model ◽

Bladder Wall ◽

Bladder Inflammation ◽

Chemically Induced ◽

Wall Injection

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Modified Yukmijihwangtang Suppresses the Production of Proinflammatory Cytokines in the Intravesical Hydrochloric Acid-Induced Cystitis Rat Model via the NF-κB Pathway

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500255 ◽

2012 ◽

Vol 40 (02) ◽

pp. 321-334 ◽

Cited By ~ 9

Author(s):

Jeong-Won Lee ◽

Sok Cheon Pak ◽

Songhee Jeon ◽

Dong-Il Kim

Keyword(s):

Medicinal Plants ◽

Rat Model ◽

In Vitro Study ◽

Intravesical Instillation ◽

Bladder Function ◽

No Production ◽

Therapeutic Effects ◽

T24 Cells ◽

Injury Group

Yukmijihwangtang (YM), a boiled extract of medicinal plants, has been prescribed for patients with kidney dysfunction in Korea; however, the mechanism underlying its therapeutic effects has not been fully elucidated. This study was conducted to evaluate the beneficial effects on bladder function by using modified YM (M-YM), which included Ulmi radicis cortex in addition to the six traditional medicinal plants in YM. Bladder irritation of the rats was caused by intravesical instillation of HCl . The animals were divided into six groups: sham group, cystitis-injury group with no treatment, cystitis-injury group with prednisolone treatment (5 mg/kg), and cystitis-injury with M-YM treatment (100, 200 or 500 mg/kg groups). Whole bladders were collected at day eight after injury. Samples were analyzed by histological and immunological examinations. An in vitro study was performed to determine whether M-YM extracts inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production and I κ B phosphorylation in a human uroepithelial cell line of T24 cells. Administration of M-YM notably improved bladder histological changes, and suppressed IL-6/TNF α production and I κ B phosphorylation in a rat model of chronic cystitis. M-YM also inhibited LPS-induced NO production and I κ B phosphorylation in T24 cells. This study suggests that administration of M-YM might be an applicable therapeutic traditional medicine for the treatment of interstitial cystitis.

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Effect of Early Sacral Neuromodulation on Bladder Function in a Rat Model of Incomplete Spinal Cord Injury Due to Focal Contusion

Neuromodulation Technology at the Neural Interface ◽

10.1111/ner.12895 ◽

2018 ◽

Vol 22 (6) ◽

pp. 697-702 ◽

Cited By ~ 1

Author(s):

Young Ju Lee ◽

Cheol Yong Yoon ◽

Min Seung Lee ◽

Byung Do Song ◽

Sang Wook Lee ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rat Model ◽

Sacral Neuromodulation ◽

Bladder Function ◽

Incomplete Spinal Cord Injury ◽

Cord Injury

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KIDNEY AND URINARY BLADDER RESPONSES OF FRESHWATER RAINBOW TROUT TO ISOSMOTIC NaCl AND NaHCO3 INFUSION

Journal of Experimental Biology ◽

10.1242/jeb.173.1.181 ◽

1992 ◽

Vol 173 (1) ◽

pp. 181-203 ◽

Cited By ~ 4

Author(s):

B. James-Curtis ◽

C. M. Wood

Keyword(s):

Rainbow Trout ◽

Urinary Bladder ◽

Metabolic Alkalosis ◽

Bladder Function ◽

Acid Base ◽

Burst Frequency ◽

Arterial Ph ◽

Acid Base Status ◽

Nacl Load ◽

Kidney Functions

The relative roles of the kidney and urinary bladder in ion, fluid and acid-base regulation were examined in freshwater rainbow trout chronically infused with either 140 mmol l-1 NaCl or 140 mmol l-1 NaHCO3 (3 ml kg-1 h-1) for 32 h. NaCl had a negligible effect on blood ionic and acid-base status, whereas NaHCO3 induced a metabolic alkalosis characterized by a rise in arterial pH and [HCO3-] and an equimolar fall in [Cl-]. Urine was collected via either an internal catheter, which bypassed bladder function, or an external urinary catheter, which collected naturally voided urine. As a percentage of the infusion rate, glomerular filtration rate increased by about 135 %, but urine flow rate (UFR) by only 80 %, reflecting increased tubular reabsorption of H2O. During NaCl infusion, virtually all of the extra Na+ and Cl- filtered was reabsorbed by the kidney tubules, resulting in an increased UFR with largely unchanged composition. During NaHCO3 infusion, tubular Na+ and Cl- reabsorption again kept pace with filtration. HCO3- reabsorption also increased, but did not keep pace with filtration; an increased flow of HCO3--rich urine resulted, which excreted about 10 % of the infused base load. At rest, fish fitted with external catheters voided in discrete bursts of about 0.85 ml kg-1 at 25 min intervals. During infusion, burst frequency increased by about 40 % and burst volume by about 20 %. Reabsorption by the bladder reduced UFR by 25 %, the excretion of Na+ and Cl- by 50 %, of K+ by 44 % and of urea by 25 %. These differences persisted on a relative basis during NaCl and NaHCO3 infusion despite the decreased residence time. However, HCO3- was neither secreted nor reabsorbed by the bladder. We conclude that the freshwater kidney functions to remove as much NaCl as possible from the urine, regardless of the NaCl load, and this role is supplemented by bladder function. The bladder plays no role in acid-base regulation during metabolic alkalosis.

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