Human Adipose Stem Cells Cell Sheet Constructs Impact Epidermal Morphogenesis in Full-Thickness Excisional Wounds
Human Adipose Stem Cells Cell Sheet Constructs Impact Epidermal Morphogenesis in Full-Thickness Excisional Wounds
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DOI：
10.1021/bm4011062
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发表时间：
2013-11-01
影响因子：
6.2
通讯作者：
Marques, A. P.
中科院分区：
文献类型：
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作者：
Cerqueira, M. T.;Pirraco, R. P.;Marques, A. P.
在以皮肤修复/再生为靶点的众多策略中，以干细胞为核心的组织工程(TE)仍然是最有前途的途径。本文提出了细胞片工程，利用特定的细胞-细胞和细胞-细胞外基质(ECM)相互作用以及随后的细胞环境，创建3D TE结构以促进全层皮肤创面的再生。人脂肪来源干细胞(HASCs)的CS在5天内使用热敏和标准细胞培养表面获得。然后，通过叠加三个CS构建基于hASCs的构建物，并将其移植到延迟愈合的全层切除小鼠皮肤伤口中。由于CS的天然粘附性，使用热响应性表面获得的构建体比从标准细胞培养表面获得的构建体更稳定。尽管没有观察到转分化现象，但两种CS生成策略都能延长hASCs的植入时间。此外，我们的研究结果表明，移植的hASCs可能主要通过与驻留细胞的旁分泌作用促进新生组织的血管形成，并广泛影响表皮的形态发生。更厚的表皮具有更高的成熟度，其特征是存在网脊状结构，以及移植结合从热响应表面获得的CS的构建物后观察到的大量毛囊，这强化了移植的hASCs的影响以及这些构建物的更高稳定性的重要性，这些构建物由紧密的细胞-细胞和细胞-ECM相互作用促进。总体而言，这项研究证实了基于CS的hASCs构建物治疗全层切除皮肤伤口的潜力，以及它们的制造条件影响皮肤再生的不同方面，如新生血管形成，但主要是表皮形态发生。
Among the wide range of strategies to target skin repair/regeneration, tissue engineering (TE) with stem cells at the forefront, remains as the most promising route. Cell sheet (CS) engineering is herein proposed, taking advantage of particular cell-cell and cell-extracellular matrix (ECM) interactions and subsequent cellular milieu, to create 3D TE constructs to promote full-thickness skin wound regeneration. Human adipose derived stem cells (hASCs) CS were obtained within five days using both thermoresponsive and standard cell culture surfaces. hASCs-based constructs were then built by superimposing three CS and transplanted into full-thickness excisional mice skin wounds with delayed healing. Constructs obtained using thermoresponsive surfaces were more stable than the ones from standard cell culture surfaces due to the natural adhesive character of the respective CS. Both CS-generating strategies lead to prolonged hASCs engraftment, although no transdifferentiation phenomena were observed. Moreover, our findings suggest that the transplanted hASCs might be promoting neotissue vascularization and extensively influencing epidermal morphogenesis, mainly through paracrine actions with the resident cells. The thicker epidermis, with a higher degree of maturation characterized by the presence of rete ridges-like structures, as well as a significant number of hair follicles observed after transplantation of the constructs combining the CS obtained from the thermoresponsive surfaces, reinforced the assumptions of the influence of the transplanted hASCs and the importance of the higher stability of these constructs promoted by cohesive cell-cell and cell-ECM interactions. Overall, this study confirmed the potential of hASCs CS-based constructs to treat full-thickness excisional skin wounds and that their fabrication conditions impact different aspects of skin regeneration, such as neovascularisation, but mainly epidermal morphogenesis.