Department of Dermatology and Allergic Diseases, University of Ulm, Ulm 89081, Germany.
Biomaterials. 2013 Mar;34(10):2501-15. doi: 10.1016/j.biomaterials.2012.12.014. Epub 2013 Jan 11.
Mesenchymal stem cells (MSCs) have properties which make them promising for the treatment of chronic non-healing wounds. A major so far unmet challenge is the efficient, safe and painless delivery of MSCs to skin wounds. Recently, a surface carrier of medical-grade silicone coated by plasma polymerisation with a thin layer of acrylic acid (ppAAc) was developed, and shown to successfully deliver MSCs to deepithelialised human dermis in vitro. Here we studied the potential of the ppAAc carrier to deliver human adipose tissue derived MSCs (AT-MSCs) to murine full-thickness excisional skin wounds in vivo. Further we investigate the mechanism of action of MSCs in accelerating wound healing in these wounds. AT-MSCs cultured on ppAAc carriers for 4 days or longer fully retained their cell surface marker expression profile, colony-forming-, differentiation- and immunosuppressive potential. Importantly, AT-MSCs delivered to murine wounds by ppAAc carriers significantly accelerated wound healing, similar to AT-MSCs delivered by intradermal injection. More than 80% of AT-MSCs were transferred from carriers to wounds in 3 days. AT-MSCs were detectable in wounds for at least 5 days after wounding. Carrier delivered AT-MSCs were demonstrated to have the capacity to down-modulate TNF-α-dependent inflammation, increase anti-inflammatory M2 macrophage numbers, and induce TGF-β(1)-dependent angiogenesis, myofibroblast differentiation and granulation tissue formation, thereby enhancing overall tissue repair.
间充质干细胞（MSCs）具有一些特性，使其成为治疗慢性难愈性伤口的有前途的方法。到目前为止，一个尚未得到满足的主要挑战是将 MSCs 有效、安全且无痛地递送到皮肤伤口。最近，开发了一种由等离子体聚合涂覆有薄薄一层丙烯酸（ppAAc）的医用级硅酮制成的表面载体，并已证明它可以成功地将 MSCs 递送到体外去上皮化的人类真皮中。在这里，我们研究了 ppAAc 载体将人脂肪组织来源的间充质干细胞（AT-MSCs）递送到体内小鼠全层切除皮肤伤口的潜力。此外，我们还研究了 MSCs 加速这些伤口愈合的作用机制。在 ppAAc 载体上培养 4 天或更长时间的 AT-MSCs 完全保留了其细胞表面标志物表达谱、集落形成、分化和免疫抑制潜能。重要的是，通过 ppAAc 载体递送到小鼠伤口中的 AT-MSCs 可显著加速伤口愈合，与通过皮内注射递送到 AT-MSCs 的效果相似。在 3 天内，超过 80%的 AT-MSCs 从载体转移到伤口。在受伤后至少 5 天内可以检测到在伤口中存在 AT-MSCs。载体递送到的 AT-MSCs 被证明能够下调 TNF-α依赖性炎症，增加抗炎 M2 巨噬细胞数量，并诱导 TGF-β（1）依赖性血管生成、肌成纤维细胞分化和肉芽组织形成，从而增强整体组织修复。
