A new era in neuromuscular junction research: current advances in self-organized and assembled in vitro models

Understanding the development and function of the human neuromuscular system is crucial for deciphering the mechanisms of neuromuscular disorders and developing effective therapies. However, limitations of animal models necessitate the development of human-specific in vitro models to study such complex diseases effectively. Here, we discuss different approaches for in vitro neuromuscular junction (NMJ) modeling: complex self-organized models that rely on the inherent abilities of cells to form NMJs based on embryonic developmental principles and assembled models that depend on integrating different cell types for controlled NMJ formation. Finally, we discuss the advantages and limitations of these models and the need for continued advancements enhanced by bioengineering approaches to deepen our understanding of human NMJ biology and pave the way for personalized medicine.