Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
PLoS One. 2013 May 14;8(5):e63075. doi: 10.1371/journal.pone.0063075. Print 2013.
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.
形态发生素 Sonic hedgehog（Shh）在修复或再生遭受缺血性损伤的组织方面具有巨大的潜力，但由于其在体内的半衰期较短，临床转化受到限制。在这里，我们描述了一种凝聚体递送系统，该系统包含 Shh，可以保护其免受降解，并至少持续释放 3 周。从凝聚体中释放的 Shh 可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，至少持续 48 小时。Shh 凝聚体在过氧化氢诱导的氧化应激环境中对心肌细胞也具有细胞保护作用。在这些研究中，Shh 凝聚体的生物活性均比游离 Shh 增强。这些结果证明了进一步研究 Shh 凝聚体在心脏修复中的体内疗效的必要性。
