Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix
Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.
Approaches for tissue and organ regeneration using decellularized extracellular matrix constructs have demonstrated some success in recent years in select applications. Craniofacial tissue regeneration with decellularized matrix constructs typically involves restoration and interactions of parenchymal and stromal components, but the specific molecular cues required to be present in the constructs to drive the desired regeneration remains unclear. A recent article by He et al. applied the tooth organ as a model to study parenchymal and stromal regeneration with a decellularized matrix. The authors found that restoring Alx3, a transcription factor involved in prenatal dentin development, in adult progenitor cells transplanted with decellularized matrix promoted regeneration of dentin with a vascularized stroma. The authors report direct targeting of promoters of Wnt3a and vascular endothelial growth factor by Alx3. Upon direct application of Wnt3a alone in surgically ablated mini-pig root canals, the authors observed regeneration of mineralized dentin and vascularized stroma by Wnt3a-responsive endogenous cells. Overall, the article suggests that a tissue engineering approach involving cell transplantation (Alx3-restored adult progenitor cells) or an acellular alternative approach involving delivery of Wnt3a (the protein target of Alx3) both present potential for dentin and pulp regeneration. In the broader context of craniofacial tissue engineering, the study suggests that approaches applying cell transplantation or leveraging endogenous cells for repair may share common pathways in certain contexts and may drive similar outcomes.
He L, Zhou J, Chen M, Lin CS, Kim SG, Zhou Y, Xiang L, Xie M, Bai H, Yao H, Shi C, Coelho PG, Bromage TG, Hu B, Tovar N, Witek L, Wu J, Chen K, Gu W, Zheng J, Sheu TJ, Zhong J, Wen J, Niu Y, Cheng B, Gong Q, Owens DM, Stanislauskas M, Pei J, Chotkowski G, Wang S, Yang G, Zegarelli DJ, Shi X, Finkel M, Zhang W, Li J, Cheng J, Tarnow DP, Zhou X, Wang Z, Jiang X, Romanov A, Rowe DW, Wang S, Ye L, Ling J, Mao J. Nat Mater. 2019;18(6):627-637.