Kabu Shushi, Gao Yue, Kwon Brian K, Labhasetwar Vinod
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Department of Orthopaedics, International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada V5Z 1M9.
J Control Release. 2015 Dec 10;219:141-154. doi: 10.1016/j.jconrel.2015.08.060. Epub 2015 Sep 4.
Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.
脊髓损伤(SCI)会导致严重的神经和病理后果,使运动、感觉和自主神经系统出现重大功能障碍。脊髓的原发性创伤性损伤引发一系列急性和慢性退行性事件,导致进一步的继发性损伤。人们已经开发出许多治疗策略,试图干预这些进行性神经退行性事件,并将对脊髓的继发性损伤降至最低。此外,人们还大力开展了再生治疗研究,以促进神经元修复,并在损伤部位建立连接。尽管这些方法在脊髓损伤的临床前动物模型中显示出了前景,但在成功转化为临床应用方面仍面临挑战。导致失败的因素包括临床前模型与人类情况之间重要的生物学和生理学差异、不符合临床实际的研究设计、治疗干预的剂量和时机差异以及剂量限制性毒性。随着对急性脊髓损伤后事件病理生物学的深入了解,有可能开发出旨在预防继发性损伤并促进神经再生恢复的综合方法,有望为这种毁灭性损伤带来有效的治疗方法。本综述的重点是突出药物治疗和给药系统以及基于细胞和组织工程的脊髓损伤治疗方法所取得的进展。