Badiola-Mateos Maider, Hervera Arnau, Del Río José Antonio, Samitier Josep
Institute for Bioengineering of Catalonia-Barcelona Institute of Science and Technology, Barcelona, Spain.
Department of Electronics and Biomedical Engineering, Faculty of Physics, Universitat de Barcelona, Barcelona, Spain.
Front Bioeng Biotechnol. 2018 Dec 11;6:194. doi: 10.3389/fbioe.2018.00194. eCollection 2018.
Movement of skeletal-muscle fibers is generated by the coordinated action of several cells taking part within the locomotion circuit (motoneurons, sensory-neurons, Schwann cells, astrocytes, microglia, and muscle-cells). Failures in any part of this circuit could impede or hinder coordinated muscle movement and cause a neuromuscular disease (NMD) or determine its severity. Studying fragments of the circuit cannot provide a comprehensive and complete view of the pathological process. We trace the historic developments of studies focused on modeling of the spinal-locomotion circuit and how bioengineered innovative technologies show advantages for an accurate mimicking of physiological conditions of spinal-locomotion circuit. New developments on compartmentalized microfluidic culture systems (cμFCS), the use of human induced pluripotent stem cells (hiPSCs) and 3D cell-cultures are analyzed. We finally address limitations of current study models and three main challenges on neuromuscular studies: (i) mimic the whole spinal-locomotion circuit including all cell-types involved and the evaluation of independent and interdependent roles of each one; (ii) mimic the neurodegenerative response of mature neurons as it occurs ; and (iii) develop, tune, implement, and combine cμFCS, hiPSC, and 3D-culture technologies to ultimately create patient-specific complete, translational, and reliable NMD model. Overcoming these challenges would significantly facilitate understanding the events taking place in NMDs and accelerate the process of finding new therapies.
骨骼肌纤维的运动是由参与运动回路的几种细胞（运动神经元、感觉神经元、施万细胞、星形胶质细胞、小胶质细胞和肌肉细胞）的协同作用产生的。该回路任何部分的故障都可能阻碍或妨碍肌肉的协调运动，并导致神经肌肉疾病（NMD）或决定其严重程度。研究该回路的片段无法全面、完整地了解病理过程。我们追溯了专注于脊髓运动回路建模的研究的历史发展，以及生物工程创新技术如何在精确模拟脊髓运动回路的生理条件方面显示出优势。分析了分隔微流控培养系统（cμFCS）、人类诱导多能干细胞（hiPSC）的使用和3D细胞培养的新进展。我们最终讨论了当前研究模型的局限性以及神经肌肉研究的三个主要挑战：（i）模拟整个脊髓运动回路，包括所有涉及的细胞类型，并评估每个细胞类型的独立和相互依赖的作用；（ii）模拟成熟神经元发生的神经退行性反应；（iii）开发、调整、实施和结合cμFCS、hiPSC和3D培养技术，最终创建患者特异性的完整、可转化和可靠的NMD模型。克服这些挑战将极大地促进对NMD中发生的事件的理解，并加速寻找新疗法的进程。
