Chohan Muhammad O
Department of Psychiatry, Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY, United States.
Department of Psychiatry, Division of Child and Adolescent Psychiatry, Columbia University, New York, NY, United States.
Front Cell Dev Biol. 2020 Mar 13;8:116. doi: 10.3389/fcell.2020.00116. eCollection 2020.
Neural repair in injury and disease presents a pressing unmet need in regenerative medicine. Due to the intrinsically reduced ability of the brain to replace lost and damaged neurons, reversing long-term cognitive and functional impairments poses a unique problem. Over the years, advancements in cellular and molecular understanding of neurogenesis mechanisms coupled with sophistication of biotechnology tools have transformed neural repair into a cross-disciplinary field that integrates discoveries from developmental neurobiology, transplantation and tissue engineering to design disease- and patient-specific remedies aimed at boosting either native rehabilitation or delivering exogenous hypoimmunogenic interventions. Advances in deciphering the blueprint of neural ontogenesis and annotation of the human genome has led to the development of targeted therapeutic opportunities that have the potential of treating the most vulnerable patient populations and whose findings from benchside suggest looming clinical translation. This review discusses how findings from studies of adult neurogenesis have informed development of interventions that target endogenous neural regenerative machineries and how advances in biotechnology, including the use of new gene-editing tools, have made possible the development of promising, complex neural transplant-based strategies. Adopting a multi-pronged strategy that is tailored to underlying neural pathology and that encompasses facilitation of endogenous regeneration, correction of patient's genomic mutations and delivery of transformed neural precursors and mature disease-relevant neuronal populations to replace injured or lost neural tissue remains no longer a fantasy.
神经损伤与疾病的修复是再生医学中亟待解决的未满足需求。由于大脑内在的替换丢失和受损神经元的能力降低，逆转长期认知和功能障碍成为一个独特的问题。多年来，对神经发生机制的细胞和分子理解的进展，以及生物技术工具的完善，已将神经修复转变为一个跨学科领域，该领域整合了发育神经生物学、移植和组织工程的发现，以设计针对疾病和患者的特定疗法，旨在促进天然修复或提供外源性低免疫原性干预措施。在解读神经发生蓝图和注释人类基因组方面的进展，已促成了靶向治疗机会的发展，这些机会有可能治疗最脆弱的患者群体，并且其在实验室的研究结果表明即将实现临床转化。本综述讨论了成体神经发生研究的结果如何为针对内源性神经再生机制的干预措施的开发提供信息，以及生物技术的进展，包括使用新的基因编辑工具，如何使基于复杂神经移植的有前景策略的开发成为可能。采用针对潜在神经病理学量身定制的多管齐下策略，包括促进内源性再生、纠正患者的基因突变以及递送转化的神经前体细胞和与疾病相关的成熟神经元群体以替代受损或丢失的神经组织，已不再是幻想。
