%0 Journal Article
%T Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix
%J -
%D 2019
%R https://doi.org/10.1038/s41563-019-0368-6
%X Cells are transplanted to regenerate an organs¡¯ parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that 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 vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/¦Â¨Ccatenin 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 that extended the processes into newly formed dentin with a structure¨Cmechanical equivalency to native dentin. Thus, the Alx3¨CWnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein
%U https://www.nature.com/articles/s41563-019-0368-6