New stem cell studies find mechanism for regenerating lost teeth

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New Delhi: Japanese researchers have identified two distinct stem cell lineages that drive tooth root and alveolar bone formation, offering key insights for future regenerative dental therapies. The team from the Institute of Science Tokyo, used genetically modified mice and lineage-tracing techniques to shed light on the cell signaling mechanisms guiding differentiation in stem cells in the developing teeth. “Our findings provide a mechanistic framework for tooth root formation and pave the way for innovative stem-cell-based regenerative therapies for dental pulp, periodontal tissues, and bone,” said Mizuki Nagata, Assistant Professor at the Institute’s Department of Periodontology. The ability to regenerate lost teeth and their surrounding bones is considered a holy grail in the field of dentistry. For decades, the gold standard for replacing a lost tooth has been a foreign object, such as a dental implant or a denture. While these solutions are quite effective, they cannot perfectly replicate a natural tooth’s structure, function, or feel. The studies, published in the journal Nature Communications, visualised and tracked tooth development in genetically modified mice. The researchers, thus, identified a previously unknown mesenchymal progenitor cell population and uncovered two distinct lineages: one strongly associated with tooth root development and the other with alveolar bone formation. The first lineage originates from cells located in the apical papilla within the epithelial root sheath — a cluster of soft tissue at the tip of the growing tooth root. These cells express CXCL12, a protein that plays a key role in bone formation within bone marrow. Through a chemical signaling pathway known as the canonical Wnt pathway, the apical papilla CXCL12-expressing cells can differentiate not only into tooth-forming odontoblasts, but also into cementum-forming cementoblasts at the elongating tooth root and even alveolar bone-forming osteoblasts under regenerative conditions. The other lineage is concentrated in the dental follicle, a sac-like structure that envelops the developing tooth and contributes to the formation of the surrounding anchoring tissue. The team found that a population of parathyroid hormone-related protein （PTHrP）-expressing cells can differentiate into cementoblasts, ligament fibroblasts, and alveolar bone-forming osteoblasts. Together, the findings advance the understanding of how teeth and alveolar bone develop in vivo, providing some much-needed clues about their intricate growing mechanisms, the team said. IANS