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推进运动神经回路再生与修复的研究:非人灵长类动物模型和成像尺度是将可注射治疗药物成功转化至临床的缺失环节。

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.

作者信息

Tsintou Magdalini, Dalamagkas Kyriakos, Makris Nikos

机构信息

Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

Center for Neural Systems Investigations, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129.

出版信息

Int J Stem Cell Res Ther. 2016;3(2). doi: 10.23937/2469-570X/1410042. Epub 2016 Oct 28.

Abstract

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.

摘要

再生与修复是中枢神经系统(CNS)创伤治疗的最终目标。中风和脊髓损伤(SCI)是两种高度常见的中枢神经系统疾病,尽管进行了大量研究且临床上急需有效治疗方法,但它们仍然无法治愈。神经工程是一个多元化的生物医学领域,采用新方法来应对这些疾病。该领域的研究主要涉及啮齿动物模型以及具有生物活性的可生物降解水凝胶。在中枢神经系统修复的临床前研究中已报道了有前景的结果,这表明开发针对脑、脊髓和周围神经损伤的新治疗方法具有巨大潜力。神经再生研究的临床转化面临几个障碍。从啮齿动物模型到人类应用的研究转化似乎存在一个关键差距,即非人类灵长类动物模型,它构成了关键的桥梁步骤。一些研究小组已开始采用在实验恒河猴模型的中风病灶中应用可注射治疗方法和多模态神经成像这一途径。了解和评估在非人类灵长类动物中用可生物降解水凝胶进行干预后受伤的脑或脊髓所经历的变化,似乎是关键的临床前研究步骤。现有的非人类灵长类动物创新模型使我们能够评估神经工程和可注射水凝胶的潜力。这些初步研究的结果将为把这项研究转化为急需的临床治疗方法铺平道路。使用连接体扫描仪的前沿成像技术代表了一项巨大进步,能够在实验动物体内对这些治疗干预进行详细的高分辨率评估。最重要的是,它们还能实现与人类的可量化且具有临床意义的关联,提高这些创新成果向临床应用转化的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8635/5870906/fcf9ae41c995/nihms947961f1.jpg

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