Improved efficacy and in vivo cellular properties of human embryonic stem cell derivative in a preclinical model of bladder pain syndrome.
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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在膀胱疼痛综合征的临床前模型中，人类胚胎干细胞衍生物的功效和体内细胞特性提高了。
DOI：
10.1038/s41598-017-09330-x
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发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Choo MS
中科院分区：
文献类型：
--
作者：
Kim A;Yu HY;Lim J;Ryu CM;Kim YH;Heo J;Han JY;Lee S;Bae YS;Kim JY;Bae DJ;Kim SY;Noh BJ;Hong KS;Han JY;Lee SW;Song M;Chung HM;Kim JK;Shin DM;Choo MS
间质性膀胱炎/膀胱痛综合征(IC/BPS)是一种以严重盆腔疼痛和尿频为特征的顽固性疾病。间充质干细胞(MSC)治疗是治疗难治性IC/BPS的一种有前途的方法。在这里，我们展示了人类胚胎干细胞(HESC)来源的多能干细胞(M-MSCs)在治疗IC/BPS方面比成人骨髓来源的多潜能干细胞(M-MSCs)更有效的治疗效果，并监测了M-MSCs在活体动物中移植的长期安全性和体内特性。经控制的hESC分化和分离过程使纯的M-MSCs表现出典型的MSC行为。在盐酸诱导的IC/BPS动物模型中，单次局部注射M-MSCs可改善IC/BPS的膀胱症状，在改善膀胱排尿功能和组织学损伤(包括尿路上皮剥脱、肥大细胞浸润、组织纤维化、细胞凋亡和内脏过敏)方面优于骨髓来源的MSCs。注射后12个月几乎没有观察到不良结果，如异常生长、肿瘤形成或免疫介导的移植排斥反应。活体内共聚焦荧光成像跟踪了移植细胞在活体动物中持续6个月以上的情况。输注的M-MSCs分化为多种细胞类型，并逐渐整合为血管样结构。本研究首次为临床前IC/BPS模型中hESC衍生物的治疗效果、长期安全性、体内分布和细胞特性的改善提供了证据。
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.
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影响因子：
6.6
作者：
Evans, R. J.;Moldwin, R. M.;Scholfield, D.
通讯作者：
Scholfield, D.
影响因子：
6.6
作者：
Jin, Hye Jin;Lee, Hyang Ju;Kim, Seong Who
通讯作者：
Kim, Seong Who
影响因子：
2.3
作者：
Jin, Long-Hu;Shin, Hwa-Yeon;Lee, Tack
通讯作者：
Lee, Tack
影响因子：
5.2
作者：
Kim, Hyung-Sik;Lee, Ji Hyun;Kim, Tae-Yoon
通讯作者：
Kim, Tae-Yoon
DOI：
10.1016/j.bbrc.2016.03.046
发表时间：
2016-04-22
影响因子：
3.1
作者：
Lim, Jisun;Kim, YongHwan;Shin, Dong-Myung
通讯作者：
Shin, Dong-Myung