PDF(Pubmed)
Abstract：
Cell therapy for the treatment of demyelinating diseases such as multiple sclerosis is hampered by poor survival of donor oligodendrocyte cell preparations, resulting in limited therapeutic outcomes. Excessive cell death leads to the release of intracellular alloantigens, which likely exacerbate local inflammation and may predispose the graft to eventual rejection. Here, we engineered innovative cell-instructive shear-thinning hydrogels (STHs) with tunable viscoelasticity and bioactivity for minimally invasive delivery of primary human oligodendrocyte progenitor cells (hOPCs) to the brain of a shiverer/rag2 mouse, a model of congenital hypomyelinating disease. The STHs enabled immobilization of prosurvival signals, including a recombinantly designed bidomain peptide and platelet-derived growth factor. Notably, STHs reduced the death rate of hOPCs significantly, promoted the production of myelinating oligodendrocytes, and enhanced myelination of the mouse brain 12 weeks post-implantation. Our results demonstrate the potential of STHs loaded with biological cues to improve cell therapies for the treatment of devastating myelopathies.
摘要：
用于治疗脱髓鞘疾病如多发性硬化症的细胞疗法因供体少突胶质细胞细胞制剂的低存活率而受到阻碍。导致治疗效果有限。过度的细胞死亡导致细胞内同种抗原的释放，这可能会加剧局部炎症，并可能使移植物最终发生排斥反应。这里,我们设计了具有可调粘弹性和生物活性的创新的细胞指导性剪切稀化水凝胶（STHs），用于将原代人少突胶质细胞祖细胞（hOPCs）微创递送至颤抖/rag2小鼠的大脑，先天性骨髓增生异常疾病的模型。STHs能够固定促生存信号，包括重组设计的bidomain肽和血小板衍生的生长因子。值得注意的是,STHs显著降低hOPCs的死亡率，促进髓鞘少突胶质细胞的产生，植入后12周，小鼠大脑的髓鞘形成增强。我们的结果证明了负载有生物线索的STHs改善细胞疗法治疗破坏性脊髓病的潜力。
