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Neural crest lineage segregation: a blueprint for periodontal regeneration.

ABSTRACT: During the recent decade, the periodontal attachment apparatus has become one of the premier areas of the body for the development of novel tissue-engineering strategies. In the present review, we describe a developmental biology approach to characterize current concepts in periodontal regeneration and to discuss strategies for future applications in periodontal therapies. To decipher the developmental make-up of the periodontal region, we have followed the path of the migratory neural crest, since it gives rise to periodontal progenitor tissues, which in turn are subjected to the influence of diverse craniofacial extracellular matrices and peptide growth factors. Based on this developmental perspective, we have conducted a systematic analysis of the factors, progenitor cells, and matrices used in current periodontal tissue-engineering approaches. We propose that the developmental history of a tissue is a highly instructive design template for the discovery of novel bioengineering tools and approaches.

SUBMITTER: Luan X

PROVIDER: S-EPMC2749262 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Neural crest lineage segregation: a blueprint for periodontal regeneration.

Luan X X Dangaria S S Ito Y Y Walker C G CG Jin T T Schmidt M K MK Galang M T MT Druzinsky R R

Journal of dental research 20090901 9

During the recent decade, the periodontal attachment apparatus has become one of the premier areas of the body for the development of novel tissue-engineering strategies. In the present review, we describe a developmental biology approach to characterize current concepts in periodontal regeneration and to discuss strategies for future applications in periodontal therapies. To decipher the developmental make-up of the periodontal region, we have followed the path of the migratory neural crest, si ...[more]

PMID: 19767574

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Project description: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+ NCSCs from human iPSCs without genome integration of reprogramming factors. To enhance survival rate upon delivery in vivo, NCSCs were centrifuged in microwell plates to form spheroids of desirable size by controlling suspension cell density. Human bone marrow mesenchymal stem cells (MSCs) were also studied for comparison. NCSC or MSC spheroids were injected into the gastrocnemius muscle with denervation injury, and the effects on NMJ formation and functional recovery were investigated. The spheroids were also co-cultured with engineered neuromuscular tissue to assess effects on NMJ formation in vitro.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.

Dataset Information

Neural crest lineage segregation: a blueprint for periodontal regeneration.

Publications

Neural crest lineage segregation: a blueprint for periodontal regeneration.

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