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A Preclinical Study of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells for Treating Detrusor Underactivity by Chronic Bladder Ischemia

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Alternative Title
A Preclinical Study of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells for Treating Detrusor Underactivity by Chronic Bladder Ischemia
Abstract
Background
The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms.

Methods
Sixteen-week-old male Sprague?Dawley rats were divided into five groups (n?=?10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0?×?105 cells (250 K, 500 K, or 1000 K; K?=?a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses.

Results
CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy.

Conclusions
Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner.
Author(s)
유환열신정현윤홍덕류채민이승운허진범임지선박주현홍기성정형민신동명주명수
Issued Date
2021
Type
Article
Keyword
Detrusor underactivityChronic bladder ischemiaMultipotent mesenchymal stem cellsEmbryonic stem cells
DOI
10.1007/s12015-021-10204-z
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8041
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2546977198&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,A%20Preclinical%20Study%20of%20Human%20Embryonic%20Stem%20Cell-Derived%20Mesenchymal%20Stem%20Cells%20for%20Treating%20Detrusor%20Underactivity%20by%20Chronic%20Bladder%20Ischemia&offset=0&pcAvailability=true
Publisher
Stem Cell Reviews and Reports
Location
미국
Language
영어
ISSN
1550-8943
Citation Volume
17
Citation Number
6
Citation Start Page
2139
Citation End Page
2152
Appears in Collections:
Medicine > Medicine
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