Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro.

Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro.
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DOI:
10.1186/s13287-015-0037-x
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发表时间:
2015-04-11
影响因子:
7.5
通讯作者:
Van de Walle GR
Van de Walle GR
中科院分区:
医学2区
文献类型:
--
作者:
Bussche L;Harman RM;Syracuse BA;Plante EL;Lu YC;Curtis TM;Ma M;Van de Walle GR

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皮肤伤口愈合受损的患病率很高,治疗困难且往往无效,从而对我们的社会产生负面的社会和经济影响。因此,迫切需要通过促进完全组织再生来改善皮肤伤口愈合的创新治疗。据报道,间充质基质细胞(MSC)提供促进伤口愈合的旁分泌信号,但(i)它们如何对靶细胞发挥作用尚不清楚,以及(ii)以受控和安全的方式供应这些MSC衍生的分泌因子的合适的递送系统不可用。本研究旨在通过使用马作为翻译模型来回答这些问题。具体而言,我们的目的是(i)评估马MSC衍生的条件培养基(CM),包含MSC分泌的所有因子,对马皮肤成纤维细胞的体外作用,这是一种成功伤口愈合的关键细胞类型,以及(ii)探索微囊化马MSC在体外将CM递送到受伤细胞的潜力。从健康马的外周血中分离MSC。在体外对来自NBL-6(马真皮成纤维细胞)系的马真皮成纤维细胞进行创伤,并在用MSC-CM或NBL-6-CM处理后评价细胞迁移和参与创伤愈合的基因的表达水平。通过使用从包封在核-壳水凝胶微胶囊中的MSC收集的CM重复这些测定。我们的显著发现是,马MSC衍生的CM刺激了马真皮成纤维细胞的迁移,并增加了它们对伤口愈合有积极贡献的基因的表达水平。此外,我们发现,封装在核壳水凝胶微胶囊中的马MSC对马真皮成纤维细胞迁移和基因表达具有相似的影响,表明MSC的微胶囊化不会干扰生物活性因子的释放。我们的研究结果表明,使用来自MSC的CM可能是受损皮肤伤口的一种有前途的新疗法,并且封装可能是有效地将CM递送到体内受伤细胞的合适方法。本文的在线版本(doi:10.1186/s13287-015-0037-x)包含补充材料,可供授权用户使用。
The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailable. The present study was designed to provide answers to these questions by using the horse as a translational model. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC-derived conditioned medium (CM), containing all factors secreted by MSCs, on equine dermal fibroblasts, a cell type critical for successful wound healing, and (ii) explore the potential of microencapsulated equine MSCs to deliver CM to wounded cells in vitro. MSCs were isolated from the peripheral blood of healthy horses. Equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line were wounded in vitro, and cell migration and expression levels of genes involved in wound healing were evaluated after treatment with MSC-CM or NBL-6-CM. These assays were repeated by using the CM collected from MSCs encapsulated in core-shell hydrogel microcapsules. Our salient findings were that equine MSC-derived CM stimulated the migration of equine dermal fibroblasts and increased their expression level of genes that positively contribute to wound healing. In addition, we found that equine MSCs packaged in core-shell hydrogel microcapsules had similar effects on equine dermal fibroblast migration and gene expression, indicating that microencapsulation of MSCs does not interfere with the release of bioactive factors. Our results demonstrate that the use of CM from MSCs might be a promising new therapy for impaired cutaneous wounds and that encapsulation may be a suitable way to effectively deliver CM to wounded cells in vivo. The online version of this article (doi:10.1186/s13287-015-0037-x) contains supplementary material, which is available to authorized users.
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