1 The Ritchie Centre, Monash Institute of Medical Research , Clayton, Victoria, Australia .
Tissue Eng Part A. 2014 Feb;20(3-4):785-98. doi: 10.1089/ten.TEA.2013.0170. Epub 2013 Nov 21.
Pelvic organ prolapse (POP) is defined as the descent of one or more of the pelvic structures into the vagina and includes uterine, vaginal vault, and anterior or posterior vaginal wall prolapse. The treatment of POP may include implantation of a synthetic mesh. However, the long-term benefit of mesh surgery is controversial due to complications such as mesh exposure or pain. The aim of this study was to use a tissue engineering (TE) approach to assess the in vivo biological and biomechanical behavior of a new gelatin/polyamide mesh, seeded with a novel source of mesenchymal stem cells in a subcutaneous rat model of wound repair.
W5C5-enriched human endometrial mesenchymal stem cells (eMSC) were seeded onto meshes (gelatin-coated polyamide knit) at 100,000 cells/cm². Meshes, with or without cells were subcutaneously implanted dorsally in immunocompromised rats for 7, 30, 60, and 90 days. Flow cytometry was used to detect DiO labeled cells after explantation. Immunohistochemical assessment of foreign body reaction and tissue integration were conducted. Total collagen and the levels of collagens type III and type I were determined. Uniaxial tensiometry was performed on explanted meshes, originally seeded with and without cells, at days 7 and 90.
Implanted meshes were well tolerated, with labeled cells detected on the mesh up to 14 days postimplantation. Meshes with cells promoted significantly more neovascularization at 7 days (p<0.05) and attracted fewer macrophages at 90 days (p<0.05). Similarly, leukocyte infiltration was significantly lower in the cell-seeded meshes at 90 days (p<0.05). Meshes with cells were generally less stiff than those without cells, after 7 and 90 days implantation.
The TE approach used in this study significantly reduced the number of inflammatory cells around the implanted mesh and promoted neovascularization. Seeding with eMSC exerts an anti-inflammatory effect and promotes wound repair with new tissue growth and minimal fibrosis, and produces mesh with greater extensibility. Cell seeding onto polyamide/gelatin mesh improves mesh biocompatibility and may be an alternative option for future treatment of POP.
盆腔器官脱垂（POP）定义为一个或多个盆腔结构下降到阴道中，包括子宫、阴道穹窿和前或后壁脱垂。POP 的治疗可能包括植入合成网片。然而，由于网片暴露或疼痛等并发症，网片手术的长期益处存在争议。本研究旨在使用组织工程（TE）方法评估一种新的明胶/聚酰胺网片在体内的生物和生物力学行为，该网片在创伤修复的皮下大鼠模型中接种了一种新型间充质干细胞来源的细胞。
将 W5C5 富集的人子宫内膜间充质干细胞（eMSC）以 100,000 个细胞/cm²的密度接种到网片（明胶涂覆的聚酰胺编织物）上。带有或不带有细胞的网片被皮下植入免疫缺陷大鼠背部，分别在 7、30、60 和 90 天进行植入。在取出后使用流式细胞术检测 DiO 标记的细胞。进行异物反应和组织整合的免疫组织化学评估。测定总胶原和胶原 III 型和 I 型的水平。对原始接种细胞和未接种细胞的网片进行单轴拉伸试验，分别在第 7 天和第 90 天进行。
植入的网片耐受良好，植入后 14 天仍能检测到标记细胞。带有细胞的网片在第 7 天（p<0.05）促进了更多的新生血管形成，在第 90 天（p<0.05）吸引了更少的巨噬细胞。同样，在第 90 天，接种细胞的网片白细胞浸润明显较低（p<0.05）。植入 7 天和 90 天后，带有细胞的网片通常比不带细胞的网片柔软。
本研究中使用的组织工程方法显著减少了植入网片周围的炎症细胞数量，并促进了新生血管形成。接种 eMSC 具有抗炎作用，并通过新组织生长和最小纤维化促进伤口修复，并产生具有更大延展性的网片。将细胞接种到聚酰胺/明胶网片上可提高网片的生物相容性，可能是未来治疗 POP 的一种替代选择。
