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人脐带基质和兔骨髓间充质干细胞在外括约肌切开术修复中的潜力。

Potential of human umbilical cord matrix and rabbit bone marrow-derived mesenchymal stem cells in repair of surgically incised rabbit external anal sphincter.

机构信息

Department of Surgery, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Dis Colon Rectum. 2009 Oct;52(10):1753-61. doi: 10.1007/DCR.0b013e3181b55112.

Abstract

PURPOSE

Anal sphincter defects and fecal incontinence are complicated surgical problems. We investigated the ability of human umbilical cord matrix (hUCM) and rabbit bone marrow (rBM) stem cells to improve anal sphincter incontinence due to induced sphincter defects without surgical repair.

METHODS

We harvested hUCM cells from human Wharton's jelly and rBM stem cells from rabbit femurs and tibias. To induce sphincter defects, we made an incision in the external anal sphincter. Rabbits were randomly allocated to 5 groups to receive either no intervention (n = 3) or injections of 10 hUCM cells in medium (10 microL RPMI-1640), rBM cells in medium, medium only, or normal saline (n = 7 per group), 2 weeks after sphincterotomy. Transplanted cells were tracked in the injured sphincters by prelabeling with bromodeoxyuridine. Electromyography was performed before and 2 weeks after the external anal sphincterotomy, and 2 weeks after cell transplantation. We also evaluated the proliferation and differentiation of injected cells with histopathologic techniques.

RESULTS

Electromyography showed significant improvement in sphincter function 2 weeks after local injection of rBM stem cells compared with pretreatment values and controls. Moderate, nonsignificant improvement was observed with hUCM cell injection. Cells with incorporated bromodeoxyuridine were detected at the site of injury after transplantation of hUCM and rBM. Histopathologic evaluation showed normal or muscle-dominant sphincter structure in all animals receiving rBM and fibrous-dominant sphincter structure in most animals receiving hUCM.

CONCLUSIONS

Stem cell injection at the site of injury can enhance contractile function of the anal sphincter without surgical repair. Transplantation of stem cells, particularly bone marrow mesenchymal cells, may provide an effective tool for treating anal sphincter injuries in humans.

摘要

目的

肛门括约肌缺陷和粪便失禁是复杂的手术问题。我们研究了人脐带基质(hUCM)和兔骨髓(rBM)干细胞在不进行手术修复的情况下改善因括约肌缺陷引起的肛门失禁的能力。

方法

我们从人 Wharton 胶中采集 hUCM 细胞,从兔股骨和胫骨中采集 rBM 干细胞。为了诱导括约肌缺陷,我们在外括约肌上做了一个切口。兔子被随机分配到 5 组,分别接受以下治疗:不干预(n = 3)或在括约肌切开后 2 周接受 10 个 hUCM 细胞在培养基(10 μL RPMI-1640)、rBM 细胞在培养基、培养基或生理盐水(每组 n = 7)的注射。通过溴脱氧尿苷预标记追踪移植细胞在损伤的括约肌中。在括约肌切开术前和术后 2 周进行肌电图检查,并在细胞移植后 2 周进行。我们还通过组织病理学技术评估注射细胞的增殖和分化。

结果

肌电图显示,与术前值和对照组相比,局部注射 rBM 干细胞后 2 周,括约肌功能明显改善。hUCM 细胞注射后观察到中度但无统计学意义的改善。移植后 hUCM 和 rBM 均可检测到掺入溴脱氧尿苷的细胞。组织病理学评估显示,所有接受 rBM 治疗的动物的括约肌结构均为正常或以肌肉为主,而大多数接受 hUCM 治疗的动物的括约肌结构均以纤维为主。

结论

在损伤部位注射干细胞可以增强肛门括约肌的收缩功能,而无需手术修复。干细胞移植,特别是骨髓间充质干细胞,可能为治疗人类肛门括约肌损伤提供一种有效工具。

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