The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats
Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In...
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| Format: | Article |
| Language: | English |
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Korean Continence Society
2018-01-01
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| Series: | International Neurourology Journal |
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| Online Access: | http://www.einj.org/upload/pdf/inj-1836014-007.pdf |
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| author | Sang Wook Lee Chae-Min Ryu Jung-Hyun Shin Daeheon Choi Aram Kim Hwan Yeul Yu Ju-Young Han Hye-Yeon Lee Jisun Lim Yong Hwan Kim Jinbeom Heo Seungun Lee Hyein Ju Sujin Kim Ki-Sung Hong Ji-Yeon Han Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo |
| author_facet | Sang Wook Lee Chae-Min Ryu Jung-Hyun Shin Daeheon Choi Aram Kim Hwan Yeul Yu Ju-Young Han Hye-Yeon Lee Jisun Lim Yong Hwan Kim Jinbeom Heo Seungun Lee Hyein Ju Sujin Kim Ki-Sung Hong Ji-Yeon Han Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo |
| author_sort | Sang Wook Lee |
| collection | DOAJ |
| description | Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage. |
| first_indexed | 2024-04-12T09:29:07Z |
| format | Article |
| id | doaj.art-4ef2badce0384251835d8fa6c008f512 |
| institution | Directory Open Access Journal |
| issn | 2093-4777 2093-6931 |
| language | English |
| last_indexed | 2024-04-12T09:29:07Z |
| publishDate | 2018-01-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj.art-4ef2badce0384251835d8fa6c008f5122022-12-22T03:38:24ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312018-01-0122Suppl 1S344510.5213/inj.1836014.007710The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in RatsSang Wook Lee0Chae-Min Ryu1Jung-Hyun Shin2Daeheon Choi3Aram Kim4Hwan Yeul Yu5Ju-Young Han6Hye-Yeon Lee7Jisun Lim8Yong Hwan Kim9Jinbeom Heo10Seungun Lee11Hyein Ju12Sujin Kim13Ki-Sung Hong14Ji-Yeon Han15Miho Song16Hyung-Min Chung17Jun Ki Kim18Dong-Myung Shin19Myung-Soo Choo20 Department of Urology, Kangwon National University School of Medicine, Chunchon, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea Department of Urology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Biochemical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaPurpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.http://www.einj.org/upload/pdf/inj-1836014-007.pdfCystitisFibrosisKetamineMultipotent stem cellsPelvic pain |
| spellingShingle | Sang Wook Lee Chae-Min Ryu Jung-Hyun Shin Daeheon Choi Aram Kim Hwan Yeul Yu Ju-Young Han Hye-Yeon Lee Jisun Lim Yong Hwan Kim Jinbeom Heo Seungun Lee Hyein Ju Sujin Kim Ki-Sung Hong Ji-Yeon Han Miho Song Hyung-Min Chung Jun Ki Kim Dong-Myung Shin Myung-Soo Choo The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats International Neurourology Journal Cystitis Fibrosis Ketamine Multipotent stem cells Pelvic pain |
| title | The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats |
| title_full | The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats |
| title_fullStr | The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats |
| title_full_unstemmed | The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats |
| title_short | The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats |
| title_sort | therapeutic effect of human embryonic stem cell derived multipotent mesenchymal stem cells on chemical induced cystitis in rats |
| topic | Cystitis Fibrosis Ketamine Multipotent stem cells Pelvic pain |
| url | http://www.einj.org/upload/pdf/inj-1836014-007.pdf |
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