Badner Anna, Siddiqui Ahad M, Fehlings Michael G
a Department of Genetics and Development , Krembil Research Institute, University Health Network , Toronto , ON , Canada.
b Institute of Medical Sciences , University of Toronto , Toronto , ON , Canada.
Expert Opin Biol Ther. 2017 May;17(5):529-541. doi: 10.1080/14712598.2017.1308481. Epub 2017 Mar 27.
Spinal cord injury (SCI) is a devastating condition, where regenerative failure and cell loss lead to paralysis. The heterogeneous and time-sensitive pathophysiology has made it difficult to target tissue repair. Despite many medical advances, there are no effective regenerative therapies. As stem cells offer multi-targeted and environmentally responsive benefits, cell therapy is a promising treatment approach. Areas covered: This review highlights the cell therapies being investigated for SCI, including Schwann cells, olfactory ensheathing cells, mensenchymal stem/stromal cells, neural precursors, oligodendrocyte progenitors, embryonic stem cells, and induced pluripotent stem cells. Through mechanisms of cell replacement, scaffolding, trophic support and immune modulation, each approach targets unique features of SCI pathology. However, as the injury is multifaceted, it is increasingly recognized that a combinatorial approach will be necessary to treat SCI. Expert opinion: Most preclinical studies, and an increasing number of clinical trials, are finding that single cell therapies have only modest benefits after SCI. These considerations, alongside issues of therapy cost-effectiveness, need to be addressed at the bench. In addition to exploring combinatorial strategies, researchers should consider cell reproducibility and storage parameters when designing animal experiments. Equally important, clinical trials must follow strict regulatory guidelines that will enable transparency of results.
脊髓损伤(SCI)是一种毁灭性疾病,再生失败和细胞丢失会导致瘫痪。其病理生理过程具有异质性且对时间敏感,这使得靶向组织修复变得困难。尽管医学取得了诸多进展,但仍没有有效的再生疗法。由于干细胞具有多靶点和对环境响应的优势,细胞疗法是一种很有前景的治疗方法。涵盖领域:本综述重点介绍了正在研究用于治疗脊髓损伤的细胞疗法,包括雪旺细胞、嗅鞘细胞、间充质干/基质细胞、神经前体细胞、少突胶质前体细胞、胚胎干细胞和诱导多能干细胞。通过细胞替代、支架构建、营养支持和免疫调节机制,每种方法都针对脊髓损伤病理的独特特征。然而,由于损伤是多方面的,人们越来越认识到采用联合方法治疗脊髓损伤将是必要的。专家观点:大多数临床前研究以及越来越多的临床试验发现,单细胞疗法在脊髓损伤后仅具有适度的益处。这些考虑因素以及治疗成本效益问题需要在实验室层面加以解决。除了探索联合策略外,研究人员在设计动物实验时应考虑细胞的可重复性和储存参数。同样重要的是,临床试验必须遵循严格的监管指南,以确保结果的透明度。