Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix

Abstract

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite common use of decellularized matrix, little is known what pivotal signals must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and VEGF. Contrasting to modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma involving VEGF signaling, but also parenchymal dentin via Wnt/β-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells extending processes into newly-formed dentin with structure-mechanical He et al.

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

“…Alternatively, recruiting periapical MSCs is highly appreciated if epigenetic regulation of odontogenic capability of PDLSCs, SCAP, or BMSCs is achieved to regenerate pulp‐dentin complex in a true sense. Identification of epigenetic factors warrants further investigation, such as Wnt3a . Actually, dental MSC inspired‐endodontic regeneration approach seems more conservative in comparison with total tooth organ regeneration strategy, which holds the highest promise for diseased tooth replacement.…”

“…Identification of epigenetic factors warrants further investigation, such as Wnt3a. 146 Actually, dental MSC inspired-endodontic regeneration approach seems more conservative in comparison with total tooth organ regeneration strategy, which holds the highest promise for dis-…”

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration

“…Specific-shaped xenogeneic matrix recellularised with allogeneic stem cells to regenerate organs is a promising strategy. Generally, these bioengineered organs are transplanted with a goal of parenchymal and stromal tissue regeneration in its natural milieu [ 4 ]. Precisely, this de-novo organogenesis model could be offered by the tooth root organ.…”

“…Precisely, this de-novo organogenesis model could be offered by the tooth root organ. The special pulp-dentin and cementum-periodontium complexes parallelly contribute to highly-mineralized parenchymal tissues and functional neurovascular stromal components [ 4 ].…”

Investigate the Odontogenic Differentiation and Dentin–Pulp Tissue Regeneration Potential of Neural Crest Cells

“…The teeth were dissected around their cervical part with a dental bur at a thickness of 2 mm. The tooth scaffolds were decellularized and decalcified in ethylene diamine tetraacetic acid (EDTA), followed by copious PBS washing (He et al, 2019). The decellularized tooth scaffolds were sterilized with ethylene oxide for in vivo transplantation.…”