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BMC Medicine:干细胞疗法有望治愈压力性尿失禁

来源:生物谷 2012-08-22 10:20

2012年8月22日 讯 /生物谷BIOON/ --一压力性尿失禁(SUI)通常在打喷嚏、咳嗽、运动甚至大笑时等情况下发生,其发生的主要原因是因为盆底肌肉太弱,膀胱压力造成泄漏。一项新的发表在BMC Medicine的研究论文表明,一种使用从羊水中分离干细胞的新技术可以使得再生受损的尿道外括约肌的肌肉,以此来预防小鼠压力性尿失禁的发生。

SUI在怀孕期间以及怀孕之后、年龄在40岁后的妇女中比较常见,有三分之一的妇女在她们的生活中会经历SUI。男性也受到影响,特别是在前列腺手术之后。尿失禁是可以治疗的,在许多情况下,减肥、减少咖啡因的摄入量、骨盆底肌肉练习、膀胱训练等手段是有非常有效的治疗尿失禁的手段。如果上述方法不起作用,那么就要采取一些更具侵入性的治疗手段,但这些治疗措施有可能引起严重的副作用。

利用干细胞再生受损坏的肌肉已被认为是一种替代手术疗法。但获取干细胞的很多方法仍带有侵入性程序,并且得到的干细胞常常数量很少。相比之下,从羊水中分离干细胞可以很容易地收集,并且具有非常低的免疫原性,这大大降低了排斥反应的可能性。韩国国立庆北大学的研究人员研究了羊膜穿刺术中人羊水分离出的干细胞对小鼠受损的尿道括约肌再生的能力。

James Yoo和Tae Gyun Kwon领导了这项研究,他们解释说,这些干细胞是间充质型的,因此在适当条件下有能力生长成为肌肉细胞,我们发现干细胞能够在小鼠体内存活七天,但在14天的时候,这些干细胞就都消失了。总之,这些干细胞能够诱导老鼠尿道括约肌的再生。(生物谷:Bioon.com)

编译自:Stem cell therapy shows promise in repairing stress urinary incontinence


 

Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model

Bum Soo Kim, So Young Chun, Jong Kil Lee, Hyun Ju Lim, Jae-Sung Bae, Ho-Yun Chung, Anthony Atala, Shay Soker, James J Yoo and Tae Gyun Kwon

Background
Stem cell injection therapies have been proposed to overcome the limited efficacy and adverse reactions of bulking agents. However, most have significant limitations, including painful procurement, requirement for anesthesia, donor site infection and a frequently low cell yield. Recently, human amniotic fluid stem cells (hAFSCs) have been proposed as an ideal cell therapy source. In this study, we investigated whether periurethral injection of hAFSCs can restore urethral sphincter competency in a mouse model.

Methods
Amniotic fluids were collected and harvested cells were analyzed for stem cell characteristics and in vitro myogenic differentiation potency. Mice underwent bilateral pudendal nerve transection to generate a stress urinary incontinence (SUI) model and received either periurethral injection of hAFSCs, periurethral injection of Plasma-Lyte (control group), or underwent a sham (normal control group). For in vivo cell tracking, cells were labeled with silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate (MNPs@SiO2 (RITC)) and were injected into the urethral sphincter region (n = 9). Signals were detected by optical imaging. Leak point pressure and closing pressure were recorded serially after injection. Tumorigenicity of hAFSCs was evaluated by implanting hAFSCs into the subcapsular space of the kidney, followed two weeks later by retrieval and histologic analysis.

Results
Flow activated cell sorting showed that hAFSCs expressed mesenchymal stem cell (MSC) markers, but no hematopoietic stem cell markers. Induction of myogenic differentiation in the hAFSCs resulted in expression of PAX7 and MYOD at Day 3, and DYSTROPHIN at Day 7. The nanoparticle-labeled hAFSCs could be tracked in vivo with optical imaging for up to 10 days after injection. Four weeks after injection, the mean LPP and CP were significantly increased in the hAFSC-injected group compared with the control group. Nerve regeneration and neuromuscular junction formation of injected hAFSCs in vivo was confirmed with expression of neuronal markers and acetylcholine receptor. Injection of hAFSCs caused no in vivo host CD8 lymphocyte aggregation or tumor formation.

Conclusions
hAFSCs displayed MSC characteristics and could differentiate into cells of myogenic lineage. Periurethral injection of hAFSCs into an SUI animal model restored the urethral sphincter to apparently normal histology and function, in absence of immunogenicity and tumorigenicity.

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