Peripheral nerve injuries are one of the most common types of traumatic damage to the nervous system. Treatment of peripheral nerve injuries aims to promote axon regrowth by imitating and improving the microenvironment for sciatic nerve regeneration. In this study, regeneration efficiency and behavior of peripheral nerves are compared under three treatment strategies: 1) transplantation of Schwann cell progenitors induced from purified neural crest stem cells; 2) implantation of a multiscale scaffold based on high‐resolution 3D printing; and 3) implantation of this bionic scaffold loading Schwann cell progenitors. The results of structural, electrophysiological, and behavioral tests demonstrate that the three treatment strategies result in different degrees of regeneration. The purified neural crest stem cells differentiate into functional Schwann cells and promote axon regeneration. The multifunctional 3D printed scaffold promotes oriented growth and myelination, and the myelinated nerve regrows with increased density and without visible scaffolds after six months. For the regeneration, scaffold treatment produces better performance than cell graft alone. Finally, it is shown that implantation of multiscale scaffolds preloaded with neural crest stem cell derived Schwann cell progenitors is the best strategy to promote peripheral nerve regeneration with improved anatomy and function among the three different strategies.
Hirschsprung's disease (HSCR) is a common congenital defect. It occurs when bowel colonization by neural crest-derived enteric nervous system (ENS) precursors is incomplete during the first trimester of pregnancy. Several sources of candidate cells have been previously studied for their capacity to regenerate the ENS, including enteric neural crest stem cells (En-NCSCs) derived from native intestine or those
Cell therapy has great promise for treating gastrointestinal motility disorders caused by
intestinal nervous system (ENS) diseases. However, appropriate sources, other than enteric
neural stem cells and human embryonic stem cells, are seldom reported. Here, we show that
neural progenitors derived from the dorsal root ganglion (DRG) of EGFP mice survived,
differentiated into enteric neurons and glia cells, migrated widely from the site of
injection, and established neuron-muscle connections following transplantation into the
distal colon of postnatal mice. The exogenous EGFP+ neurons were physiologically
functional as shown by the activity of calcium imaging. This study shows that that other
tissues besides the postnatal bowel harbor neural crest stem cells or neural progenitors
that have the potential to differentiate into functional enteric neurons in
vivo and can potentially be used for intestinal nerve regeneration. These
DRG-derived neural progenitor cells may be a choice for cell therapy of ENS disease as an
allograft. The new knowledge provided by our study is important for the development of
neural crest stem cell and cell therapy for the treatment of intestinal neuropathy.
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