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首页> 外文期刊>BJU international >Combined injection of three different lineages of early-differentiating human amniotic fluid-derived cells restores urethral sphincter function in urinary incontinence
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Combined injection of three different lineages of early-differentiating human amniotic fluid-derived cells restores urethral sphincter function in urinary incontinence

机译：三种不同谱系的早期分化人羊水衍生细胞的联合注射可恢复尿失禁中的尿道括约肌功能

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Objective To investigate whether a triple combination of early-differentiated cells derived from human amniotic fluid stem cells (hAFSCs) would show synergistic effects in urethral sphincter regeneration. Materials and Methods We early-differentiated hAFSCs into muscle, neuron and endothelial progenitor cells and then injected them into the urethral sphincter region of pudendal neurectomized ICR mice, as single-cell, double-cell or triple-cell combinations. Urodynamic studies and histological, immunohistochemical and molecular analyses were performed. Results Urodynamic study showed significantly improved leak point pressure in the triple-cell-combination group compared with the single-cell- or double-cell-combination groups. These functional results were confirmed by histological and immunohistochemical analyses, as evidenced by the formation of new striated muscle fibres and neuromuscular junctions at the cell injection site. Molecular analysis showed higher target marker expression in the retrieved urethral tissue of the triple-cell-combination group. The injection of early-differentiated hAFSCs suppressed in vivo host CD8 lymphocyte aggregations and did not form teratoma. The nanoparticle-labelled early-differentiated hAFSCs could be tracked in vivo with optical imaging for up to 14 days after injection. Conclusion Our novel concept of triple-combined early-differentiated cell therapy for the damaged sphincter may provide a viable option for incontinence treatment.
机译：目的探讨人类羊水干细胞（hAFSCs）衍生的早期分化细胞的三重组合在尿道括约肌再生中是否具有协同作用。材料和方法我们将hAFSCs早期分化为肌肉，神经元和内皮祖细胞，然后将它们以单细胞，双细胞或三细胞组合形式注射到阴部神经切除的ICR小鼠的尿道括约肌区域。进行了尿动力学研究以及组织学，免疫组织化学和分子分析。结果尿动力学研究显示，与单细胞或双细胞组合组相比，三细胞组合组的漏点压力显着改善。通过组织学和免疫组织化学分析证实了这些功能性结果，如在细胞注射部位形成了新的横纹肌纤维和神经肌肉接头所证明的。分子分析显示，三细胞结合组在取回的尿道组织中靶标表达更高。早期分化的hAFSCs的注射抑制体内宿主CD8淋巴细胞聚集，并且不形成畸胎瘤。注射后长达14天，可通过光学成像在体内追踪纳米颗粒标记的早期分化的hAFSCs。结论我们针对损伤括约肌的三联早期分化细胞疗法的新概念可能为失禁治疗提供可行的选择。

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