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Advancing research in regeneration and repair of the motor circuitry: non-human primate models and imaging scales as the missing links for successfully translating injectable therapeutics to the clinic

机译:推动和修复电机电路的研究不断发展:非人类的灵长类动物模型和影像学比例成为成功将可注射疗法转化为临床的缺失环节

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摘要

Regeneration and repair is the ultimate goal of therapeutics in trauma of the central nervous system (CNS). Stroke and spinal cord injury (SCI) are two highly prevalent CNS disorders that remain incurable, despite numerous research studies and the clinical need for effective treatments. Neural engineering is a diverse biomedical field, that addresses these diseases using new approaches. Research in the field involves principally rodent models and biologically active, biodegradable hydrogels. Promising results have been reported in preclinical studies of CNS repair, demonstrating the great potential for the development of new treatments for the brain, spinal cord and peripheral nerve injury.Several obstacles stand in the way of clinical translation of neuroregeneration research. There seems to be a key gap in the translation of research from rodent models to human applications, namely non-human primate models, which constitute a critical bridging step. Applying injectable therapeutics and multimodal neuroimaging in stroke lesions using experimental rhesus monkey models is an avenue that a few research groups have begun to embark on. Understanding and assessing the changes that the injured brain or spinal cord undergoes after an intervention with biodegradable hydrogels in non-human primates seem to represent critical preclinical research steps.Existing innovative models in non-human primates allow us to evaluate the potential of neural engineering and injectable hydrogels. The results of these preliminary studies will pave the way for translating this research into much needed clinical therapeutic approaches. Cutting edge imaging technology using Connectome scanners represents a tremendous advancement, enabling the in vivo, detailed, high-resolution evaluation of these therapeutic interventions in experimental animals. Most importantly, they also allow quantifiable and clinically meaningful correlations with humans, increasing the translatability of these innovations to the bedside.
机译:再生和修复是治疗中枢神经系统(CNS)的最终目标。中风和脊髓损伤(SCI)是两种高度流行的中枢神经系统疾病,尽管进行了许多研究研究并且需要有效的治疗方法,但仍无法治愈。神经工程是一个多样化的生物医学领域,它使用新方法来解决这些疾病。该领域的研究主要涉及啮齿动物模型和具有生物活性,可生物降解的水凝胶。在中枢神经系统修复的临床前研究中已报告了令人鼓舞的结果,证明了开发针对脑,脊髓和周围神经损伤的新疗法的巨大潜力。在神经再生研究的临床翻译中存在许多障碍。从啮齿动物模型到人类应用(即非人类灵长类动物模型)的研究翻译似乎存在关键差距,这构成了关键的桥梁步骤。使用实验性恒河猴模型在中风病变中使用可注射的治疗方法和多模式神经影像学是一些研究小组已着手的一种途径。在非人类灵长类动物中使用可生物降解水凝胶进行干预后,了解和评估受伤的大脑或脊髓所经历的变化似乎代表了关键的临床前研究步骤。非人类灵长类动物中现有的创新模型使我们能够评估神经工程和神经科学的潜力。可注射水凝胶。这些初步研究的结果将为将该研究转化为急需的临床治疗方法铺平道路。使用Connectome扫描仪的尖端成像技术代表了巨大的进步,可以对实验动物中的这些治疗干预措施进行体内,详细,高分辨率的评估。最重要的是,它们还允许与人类进行定量和临床上有意义的关联,从而增加了这些创新产品到床边的可翻译性。

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