Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model
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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-12-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/9/1/86 |
id |
doaj-cf0cec8cd6624934a868dc2de82b22b6 |
---|---|
record_format |
Article |
spelling |
doaj-cf0cec8cd6624934a868dc2de82b22b62020-11-25T01:34:19ZengMDPI AGCells2073-44092019-12-01918610.3390/cells9010086cells9010086Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat ModelJung Hyun Shin0Chae-Min Ryu1Hyein Ju2Hwan Yeul Yu3Sujin Song4Dong-Myung Shin5Myung-Soo Choo6Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaThe 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 (<i>n</i> = 10), lipopolysaccharide/protamine sulfate (LPS/PS; <i>n</i> = 10), LPS/PS + NAC (<i>n</i> = 10), LPS/PS with 25K MSC (<i>n</i> = 10), LPS/PS with 50K MSC (<i>n</i> = 10) LPS/PS + 25K MSC + NAC (<i>n</i> = 10), and LPS/PS + 50K MSC + NAC (<i>n</i> = 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 × 10<sup>4</sup> 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.https://www.mdpi.com/2073-4409/9/1/86interstitial cystitismesenchymal stem celln-acetylcysteinecombination therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jung Hyun Shin Chae-Min Ryu Hyein Ju Hwan Yeul Yu Sujin Song Dong-Myung Shin Myung-Soo Choo |
spellingShingle |
Jung Hyun Shin Chae-Min Ryu Hyein Ju Hwan Yeul Yu Sujin Song Dong-Myung Shin Myung-Soo Choo Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model Cells interstitial cystitis mesenchymal stem cell n-acetylcysteine combination therapy |
author_facet |
Jung Hyun Shin Chae-Min Ryu Hyein Ju Hwan Yeul Yu Sujin Song Dong-Myung Shin Myung-Soo Choo |
author_sort |
Jung Hyun Shin |
title |
Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model |
title_short |
Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model |
title_full |
Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model |
title_fullStr |
Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model |
title_full_unstemmed |
Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model |
title_sort |
synergistic effects of n-acetylcysteine and mesenchymal stem cell in a lipopolysaccharide-induced interstitial cystitis rat model |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-12-01 |
description |
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 (<i>n</i> = 10), lipopolysaccharide/protamine sulfate (LPS/PS; <i>n</i> = 10), LPS/PS + NAC (<i>n</i> = 10), LPS/PS with 25K MSC (<i>n</i> = 10), LPS/PS with 50K MSC (<i>n</i> = 10) LPS/PS + 25K MSC + NAC (<i>n</i> = 10), and LPS/PS + 50K MSC + NAC (<i>n</i> = 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 × 10<sup>4</sup> 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. |
topic |
interstitial cystitis mesenchymal stem cell n-acetylcysteine combination therapy |
url |
https://www.mdpi.com/2073-4409/9/1/86 |
work_keys_str_mv |
AT junghyunshin synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT chaeminryu synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT hyeinju synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT hwanyeulyu synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT sujinsong synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT dongmyungshin synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel AT myungsoochoo synergisticeffectsofnacetylcysteineandmesenchymalstemcellinalipopolysaccharideinducedinterstitialcystitisratmodel |
_version_ |
1725073145569738752 |