ArticleStem cell research & therapy2022
Intramuscular delivery of neural crest stem cell spheroids enhances neuromuscular regeneration after denervation injury.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Exploration of biomaterial and stem cell-based strategies for promoting neuronal regeneration and creating engineered 3D in-vitro disease models.Journal of translational medicine · 2025Review
- Biological Nanotherapeutics Derived From Human Umbilical Cord Mesenchymal Stem Cells: Mechanisms and Translational Potential in Multisystem Therapies for Regeneration and Oncology.International journal of nanomedicine · 2025Review
- Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.International journal of molecular sciences · 2024Review
- Epigenetic regulation and factors that influence the effect of iPSCs-derived neural stem/progenitor cells (NS/PCs) in the treatment of spinal cord injury.Clinical epigenetics · 2024Review
- Therapeutic role of neural stem cells in neurological diseases.Frontiers in bioengineering and biotechnology · 2024Review
- Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- Article
- Effects of Enamel Matrix Derivative on Cell Spheroids Made of Stem Cells Obtained from the Gingiva on Osteogenic Differentiation.Medicina (Kaunas, Lithuania) · 2023Article
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundMuscle denervation from trauma and motor neuron disease causes disabling morbidities. A limiting step in functional recovery is the regeneration of neuromuscular junctions (NMJs) for reinnervation. Stem cells have the potential to promote these regenerative processes, but current approaches have limited success, and the optimal types of stem cells remain to be determined. Neural crest stem cells (NCSCs), as the developmental precursors of the peripheral nervous system, are uniquely advantageous, but the role of NCSCs in neuromuscular regeneration is not clear. Furthermore, a cell delivery approach that can maintain NCSC survival upon transplantation is critical.
methodsWe established a streamlined protocol to derive, isolate, and characterize functional p75
resultsNCSCs cultured in spheroids displayed enhanced secretion of soluble factors involved in neuromuscular regeneration. Intramuscular transplantation of spheroids enabled long-term survival and retention of NCSCs, in contrast to the transplantation of single-cell suspensions. Furthermore, NCSC spheroids significantly improved functional recovery after four weeks as shown by gait analysis, electrophysiology, and the rate of NMJ innervation. MSC spheroids, on the other hand, had insignificant effect. In vitro co-culture of NCSC or MSC spheroids with engineered myotubes and motor neurons further evidenced improved innervated NMJ formation with NCSC spheroids.
conclusionsWe demonstrate that stem cell type is critical for neuromuscular regeneration and that NCSCs have a distinct advantage and therapeutic potential to promote reinnervation following peripheral nerve injury. Biophysical effects of spheroidal culture, in particular, enable long-term NCSC survival following in vivo delivery. Furthermore, synthetic neuromuscular tissue, or "tissues-on-a-chip," may offer a platform to evaluate stem cells for neuromuscular regeneration.
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