Lesage Flore, Roman Sabiniano, Pranpanus Savitree, Ospitalieri Simona, Zia Silvia, Jimenez Julio, MacNeil Sheila, Toelen Jaan, Deprest Jan
Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Material Science and Engineering, University of Sheffield Kroto Research Institute and Centre for Nanoscience and Technology, Sheffield, United Kingdom.
Eur J Pediatr Surg. 2018 Jun;28(3):285-292. doi: 10.1055/s-0037-1603522. Epub 2017 May 31.
The reconstruction of congenital diaphragmatic hernia or other congenital soft tissue defects often requires implants. These can be either degradable or permanent, each having their advantages. Whatever type is being used, the host response induced by implants plays a crucial role to determine the outcome. Macrophages are pivotal during implant remodeling; they are plastic and acquire in response to environmental stimuli either an inflammatory status and mediate subsequent fibrosis or a regulatory status and facilitate functional remodeling. Matrices engineered with mesenchymal stem cells (MSCs) have the capacity to modulate the host immune reaction. MSCs are believed to promote constructive remodeling of the implant through a regulatory macrophage response among others. Herein, we evaluate this potential of MSC derived from the amniotic fluid (AF-MSC), an interesting MSC type for neonatal reconstruction, on electrospun polylactic acid (PLA) scaffolds.
We seeded AF-MSC at a density of 1.10/cm on electrospun PLA matrices and determined cell viability. In vivo, we used cell-seeded or cell-free PLA matrices for subcutaneous implantation in immune competent rats. The host immune response was evaluated by histomorphometry at 14 days postoperatively.
The PLA matrix supported adherence and proliferation of AF-MSC. Fourteen days after implantation, PLA matrices were well penetrated by inflammatory cells, new blood vessels, and collagen fibers. AF-MSC-seeded scaffolds were associated with a similar response yet with a decreased number of eosinophils, increased matrix degradation and collagen fiber deposition compared with controls. The amount of total macrophages and of M2-subtype was similar for all animals.
Electrospun PLA matrices are a suitable substrate for short-term culture of AF-MSC. In rats, addition of AF-MSC to PLA matrices modulates the host response after subcutaneous implantation, yet without a difference in macrophage profile compared with control.
先天性膈疝或其他先天性软组织缺损的重建通常需要植入物。这些植入物可以是可降解的或永久性的，每种都有其优点。无论使用哪种类型，植入物诱导的宿主反应对决定结果起着关键作用。巨噬细胞在植入物重塑过程中至关重要；它们具有可塑性，并根据环境刺激获得炎症状态并介导随后的纤维化，或获得调节状态并促进功能重塑。用间充质干细胞（MSC）构建的基质有调节宿主免疫反应的能力。人们认为MSC通过调节巨噬细胞反应等方式促进植入物的建设性重塑。在此，我们评估了羊水来源的MSC（AF-MSC）这种对新生儿重建很有意义的MSC类型在电纺聚乳酸（PLA）支架上的这种潜力。
我们以1.10/cm的密度将AF-MSC接种到电纺PLA基质上，并测定细胞活力。在体内，我们将接种细胞或未接种细胞的PLA基质用于在免疫健全的大鼠皮下植入。术后14天通过组织形态计量学评估宿主免疫反应。
PLA基质支持AF-MSC的黏附和增殖。植入14天后，PLA基质被炎性细胞、新生血管和胶原纤维充分浸润。与对照组相比，接种AF-MSC的支架有类似的反应，但嗜酸性粒细胞数量减少，基质降解增加，胶原纤维沉积增加。所有动物的总巨噬细胞数量和M2亚型数量相似。
电纺PLA基质是AF-MSC短期培养的合适底物。在大鼠中，向PLA基质中添加AF-MSC可调节皮下植入后的宿主反应，但与对照组相比巨噬细胞谱无差异。
