PDF(Pubmed)
Abstract：
The healing of skin wounds, myocardial, and spinal cord injuries in salamander, newt, and axolotl amphibians, and in mouse neonates, results in scar-free regeneration, whereas injuries in adult mice heal by fibrosis and scar formation. Although both types of healing are mediated by macrophages, regeneration in these amphibians and in mouse neonates also involves innate activation of the complement system. These differences suggest that localized complement activation in adult mouse injuries might induce regeneration instead of the default fibrosis and scar formation. Localized complement activation is feasible by antigen/antibody interaction between biodegradable nanoparticles presenting α-gal epitopes (α-gal nanoparticles) and the natural anti-Gal antibody which is abundant in humans. Administration of α-gal nanoparticles into injuries of anti-Gal-producing adult mice results in localized complement activation which induces rapid and extensive macrophage recruitment. These macrophages bind anti-Gal-coated α-gal nanoparticles and polarize into M2 pro-regenerative macrophages that orchestrate accelerated scar-free regeneration of skin wounds and regeneration of myocardium injured by myocardial infarction (MI). Furthermore, injection of α-gal nanoparticles into spinal cord injuries of anti-Gal-producing adult mice induces recruitment of M2 macrophages, that mediate extensive angiogenesis and axonal sprouting, which reconnects between proximal and distal severed axons. Thus, α-gal nanoparticle treatment in adult mice mimics physiologic regeneration in amphibians. These studies further suggest that α-gal nanoparticles may be of significance in the treatment of human injuries.
摘要：
皮肤伤口的愈合，心肌,sal的脊髓损伤，newt,和axolotl两栖动物，在老鼠的新生儿中，无疤痕再生的结果，而成年小鼠的损伤通过纤维化和瘢痕形成治愈。尽管这两种类型的愈合都是由巨噬细胞介导的，这些两栖动物和小鼠新生儿的再生还涉及补体系统的先天激活。这些差异表明，成年小鼠损伤中的局部补体激活可能会诱导再生，而不是默认的纤维化和疤痕形成。通过呈递α-gal表位的生物可降解纳米颗粒(α-gal纳米颗粒)与人中丰富的天然抗Gal抗体之间的抗原/抗体相互作用,局部补体活化是可行的。向产生抗Gal的成年小鼠的损伤中施用α-gal纳米颗粒导致局部补体激活,其诱导快速和广泛的巨噬细胞募集。这些巨噬细胞结合抗Gal包被的α-gal纳米颗粒并极化成M2促再生巨噬细胞,其协调加速的皮肤伤口的无疤痕再生和由心肌梗塞(MI)损伤的心肌的再生。此外，将α-gal纳米颗粒注射到产生抗Gal的成年小鼠的脊髓损伤中，诱导M2巨噬细胞的募集，介导广泛的血管生成和轴突发芽，在近端和远端切断的轴突之间重新连接。因此，成年小鼠中的α-gal纳米颗粒治疗模拟两栖动物的生理再生。这些研究进一步表明，α-gal纳米颗粒可能在人类损伤的治疗中具有重要意义。
