Stem cell-derived conditioned media from human exfoliated deciduous teeth promote bone regeneration
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Updated: Jan 2, 2026

Establishing Organoids from Human Tooth as a Powerful Tool Toward Mechanistic Research and Regenerative Therapy
Published on: April 13, 2022
Tomoka Hiraki1, Ryo Kunimatsu1, Kengo Nakajima1
1Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Objectives:
Cleft lip and palate (CL/P) are common congenital orofacial anomalies. Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone-regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this.
Materials And Methods:
Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell- or CM-containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin-eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED-CM.
Results:
Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED-CM contained tissue-regenerating factors with roles in angiogenesis and osteogenesis.
Conclusion:
CM non-invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.

