Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair.
Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair.
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DOI：
10.1371/journal.pone.0063075
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Johnson NR;Wang Y
形态发生素Sonic hedgehog（Shh）在缺血性损伤组织的修复或再生方面具有很大的前景，然而其在体内的半衰期短限制了临床转化。在这里，我们描述了一种凝聚层递送系统，其结合了Shh，保护其免于降解，并维持其释放至少3周。从凝聚层释放的Shh刺激心脏成纤维细胞上调多种营养因子的表达，包括VEGF、SDF-1α、IGF-1和Shh本身，持续至少48小时。Shh凝聚层还证明了在过氧化氢诱导的氧化应激环境中对心肌细胞的细胞保护作用。在这些研究的每一个中，与游离Shh相比，Shh凝聚物的生物活性增强。这些结果保证了Shh凝聚层用于心脏修复的体内功效的进一步研究。
The morphogen Sonic hedgehog (Shh) holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair.
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