Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds.

Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds.
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DOI:
10.5966/sctm.2012-0088
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发表时间:
2012-11
影响因子:
6
通讯作者:
Soker S
Soker S
中科院分区:
医学2区
文献类型:
--
作者:
Skardal A;Mack D;Kapetanovic E;Atala A;Jackson JD;Yoo J;Soker S

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从羊水中获得的干细胞在培养中显示出高增殖能力和多向分化潜能。由于缺乏显着的免疫原性和羊水来源的干细胞(AFS)的能力,以调节炎症反应,我们研究了它们是否可以增加皮肤再生的小鼠模型中的伤口愈合。我们使用生物打印技术治疗nu/nu小鼠的全层皮肤伤口。将AFS细胞和骨髓来源的间充质干细胞(MSC)重悬于纤维蛋白-胶原凝胶中并“打印”在伤口部位上。在第0、7和14天,AFS细胞和MSC驱动的伤口闭合和再上皮化显著大于仅用纤维蛋白-胶原凝胶治疗的伤口的闭合和再上皮化。组织学检查显示,与MSC治疗的伤口相比,AFS细胞治疗的伤口中微血管密度和毛细血管直径增加,而仅用凝胶治疗的皮肤显示微血管量最低。然而,荧光标记的AFS细胞和MSC的追踪揭示了细胞保持短暂的并且没有永久地整合在组织中。这些观察结果表明,增加的伤口闭合率和血管生成可能是由于分泌的营养因子的递送,而不是直接的细胞-细胞相互作用。因此,我们进行了蛋白质组学分析,结果表明,AFS细胞分泌的生长因子的浓度高于MSC的浓度。同时,我们发现AFS细胞条件培养基在体外诱导内皮细胞迁移。总之,我们的研究结果表明,生物打印AFS细胞可能是大规模创伤和烧伤的有效治疗方法。
Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelalization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS ceils and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns.
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