Tissue Engineering Approaches for Motor Neuron Pathway Regeneration

During fetal development, a tightly-regulated spatio-temporal pattern of guidance cues directs and maintains motor neuron axonal growth along specific pathways to reach the target cells and tissues. However, an inflammatory environment resulting from an injury (e.g., trauma, stroke) or disease [e.g., amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and hereditary spastic paraplegia (HSP)] leads to progressive degeneration of motor neurons and destruction of axonal tracts in the adult CNS. Failure to reinstate healthy axonal connections under these conditions can severely compromise locomotor function, resulting in muscle atrophy, paralysis and death. Annually, thousands of people are diagnosed with various motor neuron related injuries and diseases in the United States, and a majority of them succumb to this condition soon after. Efforts to regenerate and accurately re-establish the lost motor neuronal networks using drug delivery, gene therapy or stem cell transplantation yielded valuable information regarding disease progression and functional circuitry formation. Recent investigations using animal models identified the role of various genes and biomolecules involved in motor neuron and related subcerebral projection neurogenesis. These results suggest that developing motor neurons could be guided by a mixture of diffusible growth factors, through varying extracellular matrix environments, to induce robust axonal outgrowth and target identification. This review discusses state-of-the-art tissue engineering approaches and techniques currently employed to promote motor neuron repair and axonal pathway regeneration under injury/ disease conditions.