Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.
Adv Healthc Mater. 2017 Jun;6(11). doi: 10.1002/adhm.201700183. Epub 2017 May 10.
Ischemic brain stroke is caused by blood flow interruption, leading to focal ischemia, neuron death, and motor, sensory, and/or cognitive dysfunctions. Angiogenesis, neovascularization from existing blood vessel, is essential for tissue growth and repair. Proangiogenic therapy for stroke is promising for preventing excess neuron death and improving functional recovery. Vascular endothelial growth factor (VEGF) is a critical factor for angiogenesis by promoting the proliferation, the survival, and the migration of endothelial cells. Here, angiogenic biomaterials to support injured brain regeneration are developed. Porous laminin (LN)-rich sponge (LN-sponge), on which histidine-tagged VEGF (VEGF-Histag) is immobilized via affinity interaction is developed. In an in vivo mouse stroke model, transplanting VEGF-Histag-LN-sponge produces remarkably stronger angiogenic activity than transplanting LN-sponge with soluble VEGF. The findings indicate that using affinity interactions to immobilize VEGF is a practical approach for developing angiogenic biomaterials for regenerating the injured brain.
缺血性脑卒中是由血流中断引起的,导致局部缺血、神经元死亡以及运动、感觉和/或认知功能障碍。血管生成,即现有血管的新生血管,对于组织生长和修复至关重要。针对脑卒中的促血管生成治疗有望预防过多的神经元死亡并改善功能恢复。血管内皮生长因子 (VEGF) 通过促进内皮细胞的增殖、存活和迁移,是血管生成的关键因素。在这里,开发了支持受损大脑再生的促血管生成生物材料。通过亲和相互作用将组氨酸标记的 VEGF(VEGF-Histag)固定在富含层粘连蛋白 (LN) 的多孔海绵 (LN-海绵) 上。在体内小鼠脑卒中模型中,移植 VEGF-Histag-LN-海绵比移植含有可溶性 VEGF 的 LN-海绵产生更强的促血管生成活性。这些发现表明,使用亲和相互作用固定 VEGF 是开发用于再生受损大脑的促血管生成生物材料的一种实用方法。