The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

被引：24

作者：

Lee, Sang Wook ^{[1
]}

Ryu, Chae-Min ^{[2
,3
]}

Shin, Jung-Hyun ^{[2
]}

Choi, Daeheon ^{[2
]}

Kim, Aram ^{[4
]}

Yu, Hwan Yeul ^{[2
,3
]}

Han, Ju-Young ^{[2
,3
]}

Lee, Hye-Yeon ^{[3
,5
]}

Lim, Jisun ^{[3
,5
]}

Kim, Yong Hwan ^{[3
,5
]}

Heo, Jinbeom ^{[3
,5
]}

Lee, Seungun ^{[3
,5
]}

Ju, Hyein ^{[3
,5
]}

Kim, Sujin ^{[3
,5
]}

Hong, Ki-Sung ^{[6
]}

Han, Ji-Yeon ^{[7
]}

Song, Miho ^{[2
]}

Chung, Hyung-Min ^{[6
,8
]}

Kim, Jun Ki ^{[9
]}

Shin, Dong-Myung ^{[3
,5
]}

Choo, Myung-Soo ^{[2
]}

机构：

[1] Kangwon Natl Univ, Sch Med, Dept Urol, Chunchon, South Korea

[2] Univ Ulsan, Coll Med, Dept Urol, Asan Med Ctr, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

[3] Univ Ulsan, Coll Med, Dept Biochem Sci, Asan Med Ctr, Seoul, South Korea

[4] Konkuk Univ, Sch Med, Dept Urol, Med Ctr, Seoul, South Korea

[5] Univ Ulsan, Coll Med, Dept Physiol, Asan Med Ctr, Seoul, South Korea

[6] Konkuk Univ, Sch Med, Dept Stem Cell Biol, Seoul, South Korea

[7] Pusan Natl Univ, Yangsan Hosp, Dept Urol, Sch Med, Busan, South Korea

[8] Mirae Cell Bio Co LTD, Seoul, South Korea

[9] Univ Ulsan, Coll Med, Asan Inst Life Sci, Asan Med Ctr, Seoul, South Korea

来源：

INTERNATIONAL NEUROUROLOGY JOURNAL | 2018年 / 22卷

基金：

新加坡国家研究基金会;

关键词：

Cystitis; Fibrosis; Ketamine; Multipotent stem cells; Pelvic pain; KETAMINE-INDUCED CYSTITIS; UMBILICAL-CORD BLOOD; REGENERATIVE MEDICINE; PAIN SYNDROME; MODEL; DYSFUNCTION; MECHANISMS; STRATEGIES; FIBROSIS; BLADDER;

D O I：

10.5213/inj.1836014.007

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 1x10(6) 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 (1x10(5) 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 (1x10(5)) 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.

引用

页码：S34 / S45

页数：12

共 36 条

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