Age-dependent decline in dental pulp regeneration after pulpectomy in dogs.
The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, pulp regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in pulp regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.
Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan. Electronic address: iohara@ncgg.go.jp.
Koichiro
K
Iohara
Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan. Electronic address: murakami@ncgg.go.jp.
Masashi
M
Murakami
Department of Endodontology, School of Dentistry, Aichi-gakuin University, Nagoya, Japan. Electronic address: kazukun@dpc.aichi-gakuin.ac.jp.
Kazuhiko
K
Nakata
Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan. Electronic address: misako@ncgg.go.jp.
Misako
M
Nakashima
D000375:Aging; D000818:Animals; D017077:Culture Media, Conditioned; D003782:Dental Pulp / Q000166:cytology / Q000502:physiology*; D004285:Dogs; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology; D011670:Pulpectomy; D012038:Regeneration / Q000502:physiology*
D017077:Culture Media, Conditioned; D016179:Granulocyte Colony-Stimulating Factor
Aging; Autologous cell transplantation; Dental pulp stem cells (DPSCs); Granulocyte colony-stimulating factor (G-CSF); Pulp/dentin regeneration; Pulpectomy