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在小鼠模型中用人脂肪来源干细胞进行筋膜组织工程:对盆底重建的意义

Fascia tissue engineering with human adipose-derived stem cells in a murine model: Implications for pelvic floor reconstruction.

作者信息

Hung Man-Jung, Wen Mei-Chin, Huang Ying-Ting, Chen Gin-Den, Chou Min-Min, Yang Vivian Cheng

机构信息

Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University, School of Medicine, Taichung, Taiwan.

Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan.

出版信息

J Formos Med Assoc. 2014 Oct;113(10):704-15. doi: 10.1016/j.jfma.2013.04.017. Epub 2013 Jun 19.

DOI:10.1016/j.jfma.2013.04.017
PMID:23791005
Abstract

BACKGROUND/PURPOSE: Mesh-augmented vaginal surgery for treatment of pelvic organ prolapse (POP) does not meet patients' needs. This study aims to test the hypothesis that fascia tissue engineering using adipose-derived stem cells (ADSCs) might be a potential therapeutic strategy for reconstructing the pelvic floor.

METHODS

Human ADSCs were isolated, differentiated, and characterized in vitro. Both ADSCs and fibroblastic-differentiated ADSCs were used to fabricate tissue-engineered fascia equivalents, which were then transplanted under the back skin of experimental nude mice.

RESULTS

ADSCs prepared in our laboratory were characterized as a group of mesenchymal stem cells. In vitro fibroblastic differentiation of ADSCs showed significantly increased gene expression of cellular collagen type I and elastin (p < 0.05) concomitantly with morphological changes. By contrast, ADSCs cultured in control medium did not demonstrate these changes. Both of the engrafted fascia equivalents could be traced up to 12 weeks after transplantation in the subsequent animal study. Furthermore, the histological outcomes differed with a thin (111.0 ± 19.8 μm) lamellar connective tissue or a thick (414.3 ± 114.9 μm) adhesive fibrous tissue formation between the transplantation of ADSCs and fibroblastic-differentiated ADSCs, respectively. Nonetheless, the implantation of a scaffold without cell seeding (the control group) resulted in a thin (102.0 ± 17.1 μm) fibrotic band and tissue contracture.

CONCLUSION

Our results suggest the ADSC-seeded implant is better than the implant alone in enhancing tissue regeneration after transplantation. ADSCs with or without fibroblastic differentiation might have a potential but different role in fascia tissue engineering to repair POP in the future.

摘要

背景/目的:网片增强阴道手术治疗盆腔器官脱垂(POP)不能满足患者需求。本研究旨在验证以下假设:利用脂肪来源干细胞(ADSCs)进行筋膜组织工程可能是重建盆底的一种潜在治疗策略。

方法

体外分离、分化并鉴定人ADSCs。将ADSCs和成纤维细胞分化的ADSCs用于制备组织工程筋膜等效物,然后将其移植到实验裸鼠的背部皮肤下。

结果

我们实验室制备的ADSCs被鉴定为一组间充质干细胞。ADSCs的体外成纤维细胞分化显示,细胞I型胶原蛋白和弹性蛋白的基因表达显著增加(p < 0.05),同时伴有形态学变化。相比之下,在对照培养基中培养的ADSCs未表现出这些变化。在随后的动物研究中,两种植入的筋膜等效物在移植后12周均可追踪到。此外,ADSCs和成纤维细胞分化的ADSCs移植后,组织学结果有所不同,分别形成了薄的(111.0±19.8μm)层状结缔组织或厚的(414.3±114.9μm)粘连纤维组织。尽管如此,未接种细胞的支架植入(对照组)导致形成薄的(102.0±17.1μm)纤维化带和组织挛缩。

结论

我们的结果表明,接种ADSCs的植入物在移植后促进组织再生方面优于单独的植入物。具有或不具有成纤维细胞分化的ADSCs在未来筋膜组织工程修复POP中可能具有潜在但不同的作用。

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