title: Isolation of a stable subpopulation of mobilized dental pulp stem cells (MDPSCs) with high proliferation, migration, and regeneration potential is independent of age.
abstract: Insights into the understanding of the influence of the age of MSCs on their cellular responses and regenerative potential are critical for stem cell therapy in the clinic. We have isolated dental pulp stem cells (DPSCs) subsets based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs) from young and aged donors. The aged MDPSCs were efficiently enriched in stem cells, expressing high levels of trophic factors with high proliferation, migration and anti-apoptotic effects compared to young MDPSCs. In contrast, significant differences in those properties were detected between aged and young colony-derived DPSCs. Unlike DPSCs, MDPSCs showed a small age-dependent increase in senescence-associated β-galactosidase (SA-β-gal) production and senescence markers including p16, p21, Interleukin (IL)-1β, -6, -8, and Groα in long-term culture. There was no difference between aged and young MDPSCs in telomerase activity. The regenerative potential of aged MDPSCs was similar to that of young MDPSCs in an ischemic hindlimb model and an ectopic tooth root model. These results demonstrated that the stem cell properties and the high regenerative potential of MDPSCs are independent of age, demonstrating an immense utility for clinical applications by autologous cell transplantation in dental pulp regeneration and ischemic diseases.
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan; Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Iohara
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan; Department of Pediatric Dentistry, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan; Department of Endodontics, School of Dentistry, Aichi-g akuin University, Nagoya, Aichi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Takeuchi
authors.affiliation: Department of Biochemistry and Division of Disease Models, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-gakuin University, Nagoya, Aichi, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kurita
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Aichi, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D003782:Dental Pulp / Q000166:cytology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D001616:beta-Galactosidase