Local injection of bone marrow progenitor cells for the treatment of anal sphincter injury: in-vitro expanded versus minimally-manipulated cells.
Local injection of bone marrow progenitor cells for the treatment of anal sphincter injury: in-vitro expanded versus minimally-manipulated cells.
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DOI：
10.1186/s13287-016-0344-x
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发表时间：
2016-06-21
影响因子：
7.5
通讯作者：
Pessina F
中科院分区：
文献类型：
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作者：
Mazzanti B;Lorenzi B;Borghini A;Boieri M;Ballerini L;Saccardi R;Weber E;Pessina F
肛门失禁是一种致残性疾病，对大量患者的生活质量产生不利影响，主要是肛门括约肌病变。在先前的实验工作中，体外扩增的骨髓（BM）来源的间充质干细胞（MSC）被证明可以在大鼠临床前模型中增强损伤后的括约肌愈合和初级修复。在本文中，我们研究了未扩增的BM单核细胞（MNC）是否也可能是有效的。将32只大鼠分为3组，分别行括约肌切开术和括约肌修复术（SR），一期缝合肛门括约肌，同时括约肌内注射生理盐水（CTR）、体外扩增的MSC或微操作的MNC;第4组行假手术。在第30天，进行组织学、形态学、体外收缩性和功能分析。与CTR相比，用MSC和MNC治疗改善SR后的肌肉再生并增加肛门括约肌的收缩功能（p < 0.05）。在所使用的两种BM干细胞类型之间未观察到显著差异。GFP阳性细胞（MSC和MNC）在注射后30天仍保持在病变部位附近。在本研究中，我们在临床前模型中证明了最低限度操作的BM-MNC与体外扩增的MSC一样有效，用于肛门括约肌损伤的恢复，随后进行初次括约肌修复。这些结果可能作为一个基础，提高干细胞疗法在人类肛门失禁治疗的临床应用。
Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions. In a previous experimental work, in-vitro expanded bone marrow (BM)-derived mesenchymal stem cells (MSC) were demonstrated to enhance sphincter healing after injury and primary repair in a rat preclinical model. In the present article we investigated whether unexpanded BM mononuclear cells (MNC) may also be effective. Thirty-two rats, divided into groups, underwent sphincterotomy and repair (SR) with primary suture of anal sphincters plus intrasphincteric injection of saline (CTR), or of in-vitro expanded MSC, or of minimally manipulated MNC; moreover, the fourth group underwent sham operation. At day 30, histologic, morphometric, in-vitro contractility, and functional analysis were performed. Treatment with both MSC and MNC improved muscle regeneration and increased contractile function of anal sphincters after SR compared with CTR (p < 0.05). No significant difference was observed between the two BM stem cell types used. GFP-positive cells (MSC and MNC) remained in the proximity of the lesion site up to 30 days post injection. In the present study we demonstrated in a preclinical model that minimally manipulated BM-MNC were as effective as in-vitro expanded MSC for the recovery of anal sphincter injury followed by primary sphincter repair. These results may serve as a basis for improving clinical applications of stem cell therapy in human anal incontinence treatment.