Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Engineering Medicine, Beihang University, Beijing, China.
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
J Cereb Blood Flow Metab. 2023 Sep;43(9):1456-1474. doi: 10.1177/0271678X231179544. Epub 2023 May 31.
Despite the high prevalence, stroke remains incurable due to the limited regeneration capacity in the central nervous system. Neuronal replacement strategies are highly diverse biomedical fields that attempt to replace lost neurons by utilizing exogenous stem cell transplants, biomaterials, and direct neuronal reprogramming. Although these approaches have achieved encouraging outcomes mostly in the rodent stroke model, further preclinical validation in non-human primates (NHP) is still needed prior to clinical trials. In this paper, we briefly review the recent progress of promising neuronal replacement therapy in NHP stroke studies. Moreover, we summarize the key characteristics of the NHP as highly valuable translational tools and discuss (1) NHP species and their advantages in terms of genetics, physiology, neuroanatomy, immunology, and behavior; (2) various methods for establishing NHP focal ischemic models to study the regenerative and plastic changes associated with motor functional recovery; and (3) a comprehensive analysis of experimentally and clinically accessible outcomes and a potential adaptive mechanism. Our review specifically aims to facilitate the selection of the appropriate NHP cortical ischemic models and efficient prognostic evaluation methods in preclinical stroke research design of neuronal replacement strategies.
尽管中风的发病率很高，但由于中枢神经系统的再生能力有限，目前仍然无法治愈。神经元替代策略是高度多样化的生物医学领域，旨在通过利用外源性干细胞移植、生物材料和直接神经元重编程来替代丢失的神经元。尽管这些方法在啮齿动物中风模型中取得了令人鼓舞的结果，但在临床试验之前，仍需要在非人类灵长类动物（NHP）中进行进一步的临床前验证。本文简要综述了 NHP 中风研究中具有前景的神经元替代治疗的最新进展。此外，我们总结了 NHP 的关键特征，将其作为高度有价值的转化工具，并讨论了：（1）NHP 物种及其在遗传学、生理学、神经解剖学、免疫学和行为方面的优势；（2）用于建立 NHP 局灶性缺血模型的各种方法，以研究与运动功能恢复相关的再生和可塑性变化；以及（3）对实验和临床可及的结果以及潜在的适应机制进行全面分析。我们的综述旨在为神经元替代策略的临床前中风研究设计中选择合适的 NHP 皮质缺血模型和有效的预后评估方法提供便利。
