Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Neurosurgery. 2021 Mar 15;88(4):733-745. doi: 10.1093/neuros/nyaa531.
Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts. In the present work, we review the major clinical trials of cell therapy for stroke and highlight a mechanistic shift between the earliest studies, which aimed to replace dead and damaged neurons, and later ones that focused on exploiting the various neuromodulatory effects afforded by stem cells. We discuss why both mechanisms are worth pursuing and emphasize the means through which cell replacement can still be achieved.
细胞疗法已被广泛认为是一种有前途的策略,可以促进中风幸存者的康复。然而,尽管有大量令人鼓舞的临床前数据,但成功的临床转化仍然难以实现。随着该领域的不断发展,重新审视以前临床试验的预期机制非常重要,因为这可以为未来的临床前和转化研究提供信息。在本工作中,我们回顾了细胞疗法治疗中风的主要临床试验,并强调了最早的研究旨在替代死亡和受损的神经元,而后来的研究则侧重于利用干细胞提供的各种神经调节作用之间的机制转变。我们讨论了为什么这两种机制都值得研究,并强调了通过细胞替代仍然可以实现的方法。