Exploring the Potential for Biomaterials to Improve the Development of Spinal Motor Neurons from Induced Pluripotent Stem Cells

Abstract

Neuromuscular diseases (NMDs) are primarily caused by progressive degeneration of motor neurons that leads to skeletal muscle denervation. The physiological complexity and cellular heterogeneity of individual motor units make understanding the underlying pathological mechanisms of NMDs difficult. Moreover, the demonstrable species specificity of neuromuscular synapse structure and function underscores the need to develop reliable human models of neuromuscular physiology with which to study disease etiology and test the efficacy of novel therapeutics. In this regard, human-induced pluripotent stem cells (hiPSCs) represent a valuable tool for developing such models. However, the lack of cellular diversity and transcriptomic immaturity of motor neurons derived from iPSCs has so far limited their downstream applications. To address this shortcoming, biomaterials such as 3D biopolymer scaffolds and biocompatible nanoparticles have been investigated for their ability to improve current neuronal differentiation protocols. In this review, we summarize current efforts and limitations associated with the use of functional biomaterials to increase the physiological relevance of stem cell-derived motor neurons. We also suggest potential future directions for research using biomaterials to overcome outstanding issues related to stem cell-based neuromuscular tissue production for use in NMD modeling applications.