University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Guimarães, Portugal.
Biomaterials. 2012 Sep;33(27):6345-54. doi: 10.1016/j.biomaterials.2012.05.050. Epub 2012 Jun 12.
The regenerative capacity of injured adult central nervous system (CNS) tissue is very limited. Specifically, traumatic spinal cord injury (SCI) leads to permanent loss of motor and sensory functions below the site of injury, as well as other detrimental complications. A potential regenerative strategy is stem cell transplantation; however, cell survival is typically less than 1%. To improve cell survival, stem cells can be delivered in a biomaterial matrix that provides an environment conducive to survival after transplantation. One major challenge in this approach is to define the biomaterial and cell strategies in vitro. To this end, we investigated both peptide-modification of gellan gum and olfactory ensheathing glia (OEG) on neural stem/progenitor cell (NSPC) fate. To enhance cell adhesion, the gellan gum (GG) was modified using Diels-Alder click chemistry with a fibronectin-derived synthetic peptide (GRGDS). Amino acid analysis demonstrated that approximately 300 nmol of GRGDS was immobilized to each mg of GG. The GG-GRGDS had a profound effect on NSPC morphology and proliferation, distinct from that of NSPCs in GG alone, demonstrating the importance of GRGDS for cell-GG interaction. To further enhance NSPC survival and outgrowth, they were cultured with OEG. Here NSPCs interacted extensively with OEG, demonstrating significantly greater survival and proliferation relative to monocultures of NSPCs. These results suggest that this co-culture strategy of NSPCs with OEG may have therapeutic benefit for SCI repair.
受伤的成人中枢神经系统 (CNS) 组织的再生能力非常有限。具体来说，创伤性脊髓损伤 (SCI) 会导致损伤部位以下的运动和感觉功能永久丧失，以及其他有害的并发症。一种潜在的再生策略是干细胞移植；然而，细胞存活率通常不到 1%。为了提高细胞存活率，可以将干细胞递送至生物材料基质中，该基质为移植后细胞的存活提供有利环境。该方法的一个主要挑战是在体外定义生物材料和细胞策略。为此，我们研究了对神经干细胞/祖细胞 (NSPC) 命运的凝胶多糖的肽修饰和嗅鞘细胞 (OEG)。为了增强细胞粘附，使用 Diels-Alder 点击化学将源自纤连蛋白的合成肽 (GRGDS) 修饰凝胶多糖 (GG)。氨基酸分析表明，大约 300 nmol 的 GRGDS 固定到每毫克 GG 上。GG-GRGDS 对 NSPC 形态和增殖有深远的影响，与单独的 GG 中的 NSPC 不同，这表明 GRGDS 对细胞-GG 相互作用很重要。为了进一步提高 NSPC 的存活率和生长，将它们与 OEG 共培养。在这里，NSPC 与 OEG 广泛相互作用，与 NSPC 的单核培养相比，表现出显著更高的存活率和增殖率。这些结果表明，这种与 OEG 共培养的 NSPC 策略可能对 SCI 修复具有治疗益处。
