Neuromuscular junction (NMJ) research is essential to advance the understanding of neuromuscular pathophysiology and the development of new therapies for diseases associated with NMJ dysfunction. In vivo, the microenvironment of NMJ has a significant impact on the formation and maturation of NMJ via neurotrophic factors and differentiation factors that are secreted as a result of the dialogue between muscle fibers and motor neurons.
In an article published in April 2021, a group of European researchers including researchers from the institute, showed that functional NMJ could develop in vitro in a co-culture of immortalized human myoblasts and motor neurons, from explants rat embryo spinal cord, using culture medium free of serum and neurotrophic or growth factors.
The aim of this study was to assess how functional NMJ were able to develop in this co-culture devoid of exogenous neuronal growth factors. To do this, the authors used an ELISA-based microarray to compare the composition of soluble growth factors secreted endogenously in this co-culture with a culture of a-neural muscle. The levels of seven neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-3 binding protein (IGFBP-3), growth similar to insulin-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) and vascular endothelial growth factor (VEGF)] were higher in the supernatant of the NMJ culture compared to those found in the supernatant of the α-neural muscle culture.
These results indicate that the dialogue between myotubes and motor neurons promotes the secretion of soluble growth factors that contribute to the local microenvironment, thus providing a favorable regenerative niche for the formation and maturation of NMJ.
