Mesh : Animals Astrocytes / metabolism Neurons Signal Transduction Spinal Cord / metabolism Spinal Cord Injuries

来  源:   DOI:10.1038/s41393-024-00969-8

Abstract:
METHODS: A Systematic Review OBJECTIVES: To determine the therapeutic efficacy of in vivo reprogramming of astrocytes into neuronal-like cells in animal models of spinal cord injury (SCI).
METHODS: PRISMA 2020 guidelines were utilized, and search engines Medline, Web of Science, Scopus, and Embase until June 2023 were used. Studies that examined the effects of converting astrocytes into neuron-like cells with any vector in all animal models were included, while conversion from other cells except for spinal astrocytes, chemical mechanisms to provide SCI models, brain injury population, and conversion without in-vivo experience were excluded. The risk of bias was calculated independently.
RESULTS: 5302 manuscripts were initially identified and after eligibility assessment, 43 studies were included for full-text analysis. After final analysis, 13 manuscripts were included. All were graded as high-quality assessments. The transduction factors Sox2, Oct4, Klf4, fibroblast growth factor 4 (Fgf4) antibody, neurogenic differentiation 1 (Neurod1), zinc finger protein 521 (Zfp521), ginsenoside Rg1, and small molecules (LDN193189, CHIR99021, and DAPT) could effectively reprogramme astrocytes into neuron-like cells. The process was enhanced by p21-p53, or Notch signaling knockout, valproic acid, or chondroitin sulfate proteoglycan inhibitors. The type of mature neurons was both excitatory and inhibitory.
CONCLUSIONS: Astrocyte reprogramming to neuronal-like cells in an animal model after SCI appears promising. The molecular and functional improvements after astrocyte reprogramming were demonstrated in vivo, and further investigation is required in this field.
摘要:
方法:系统评价目的:为了确定在脊髓损伤(SCI)动物模型中星形胶质细胞体内重编程为神经元样细胞的治疗效果。
方法:使用了PRISMA2020指南,搜索引擎Medline,WebofScience,Scopus,和Embase直到2023年6月才被使用。包括在所有动物模型中检查用任何载体将星形胶质细胞转化为神经元样细胞的作用的研究。除了脊髓星形胶质细胞外,其他细胞的转化,提供SCI模型的化学机制,脑损伤人群,和转换没有体内经验被排除。独立计算偏倚风险。
结果:最初确定了5302份手稿,经过资格评估,43项研究纳入全文分析。经过最后分析,其中包括13份手稿。所有这些都被评为高质量评估。转导因子Sox2,Oct4,Klf4,成纤维细胞生长因子4(Fgf4)抗体,神经源性分化1(Neurod1),锌指蛋白521(Zfp521),人参皂苷Rg1和小分子(LDN193189,CHIR99021和DAPT)可以有效地将星形胶质细胞重新编程为神经元样细胞。p21-p53或Notch信号敲除增强了该过程,丙戊酸,或硫酸软骨素蛋白聚糖抑制剂。成熟神经元的类型为兴奋性和抑制性。
结论:在SCI后的动物模型中,星形胶质细胞重编程为神经元样细胞似乎很有希望。在体内证明了星形胶质细胞重编程后的分子和功能改善,需要对此领域进行进一步调查。
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