Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem...

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Autores principales:	Aram Kim, Hwan Yeul Yu, Jisun Lim, Chae-Min Ryu, Yong Hwan Kim, Jinbeom Heo, Ju-Young Han, Seungun Lee, Yoon Sung Bae, Jae Young Kim, Dong-Jun Bae, Sang-Yeob Kim, Byeong-Joo Noh, Ki-Sung Hong, Ji-Yeon Han, Sang Wook Lee, Miho Song, Hyung-Min Chung, Jun Ki Kim, Dong-Myung Shin, Myung-Soo Choo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d4a5c86dae849c1b92c8adbad8ea9a7
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spelling	oai:doaj.org-article:6d4a5c86dae849c1b92c8adbad8ea9a72021-12-02T15:05:16ZImproved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome10.1038/s41598-017-09330-x2045-2322https://doaj.org/article/6d4a5c86dae849c1b92c8adbad8ea9a72017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09330-xhttps://doaj.org/toc/2045-2322Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.Aram KimHwan Yeul YuJisun LimChae-Min RyuYong Hwan KimJinbeom HeoJu-Young HanSeungun LeeYoon Sung BaeJae Young KimDong-Jun BaeSang-Yeob KimByeong-Joo NohKi-Sung HongJi-Yeon HanSang Wook LeeMiho SongHyung-Min ChungJun Ki KimDong-Myung ShinMyung-Soo ChooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aram Kim Hwan Yeul Yu Jisun Lim Chae-Min Ryu Yong Hwan Kim Jinbeom Heo Ju-Young Han Seungun Lee Yoon Sung Bae Jae Young Kim Dong-Jun Bae Sang-Yeob Kim Byeong-Joo Noh Ki-Sung Hong Ji-Yeon Han Sang Wook Lee Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
description	Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.
format	article
author	Aram Kim Hwan Yeul Yu Jisun Lim Chae-Min Ryu Yong Hwan Kim Jinbeom Heo Ju-Young Han Seungun Lee Yoon Sung Bae Jae Young Kim Dong-Jun Bae Sang-Yeob Kim Byeong-Joo Noh Ki-Sung Hong Ji-Yeon Han Sang Wook Lee Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo
author_facet	Aram Kim Hwan Yeul Yu Jisun Lim Chae-Min Ryu Yong Hwan Kim Jinbeom Heo Ju-Young Han Seungun Lee Yoon Sung Bae Jae Young Kim Dong-Jun Bae Sang-Yeob Kim Byeong-Joo Noh Ki-Sung Hong Ji-Yeon Han Sang Wook Lee Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo
author_sort	Aram Kim
title	Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
title_short	Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
title_full	Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
title_fullStr	Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
title_full_unstemmed	Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
title_sort	improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6d4a5c86dae849c1b92c8adbad8ea9a7
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Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome

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