Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration.
Human dental pulp stem/progenitor cells (hDPSCs) are attractive candidates for regenerative therapy because they can be easily expanded to generate colony-forming unit-fibroblasts (CFU-Fs) on plastic and the large cell numbers required for transplantation. However, isolation based on adherence to plastic inevitably changes the surface marker expression and biological properties of the cells. Consequently, little is currently known about the original phenotypes of tissue precursor cells that give rise to plastic-adherent CFU-Fs. To better understand the in vivo functions and translational therapeutic potential of hDPSCs and other stem cells, selective cell markers must be identified in the progenitor cells. Here, we identified a dental pulp tissue-specific cell population based on the expression profiles of 2 cell-surface markers LNGFR (CD271) and THY-1 (CD90). Prospectively isolated, dental pulp-derived LNGFR(Low+)THY-1(High+) cells represent a highly enriched population of clonogenic cells--notably, the isolated cells exhibited long-term proliferation and multilineage differentiation potential in vitro. The cells also expressed known mesenchymal cell markers and promoted new bone formation to heal critical-size calvarial defects in vivo. These findings suggest that LNGFR(Low+)THY-1(High+) dental pulp-derived cells provide an excellent source of material for bone regenerative strategies.
Department of Physiology, Keio University School of Medicine, Tokyo, Japan Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan.
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Yasui
Department of Physiology, Keio University School of Medicine, Tokyo, Japan Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
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Mabuchi
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
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Toriumi
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
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Ebine
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan Division of Molecular and Regenerative Prosthodontics, Graduate School of Dentistry, Tohoku University, Miyagi, Japan.
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Niibe
Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK.
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Houlihan
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.
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Morikawa
Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan.
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Onizawa
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.
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Kawana
Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
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Akazawa
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
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Suzuki
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan.
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Nakagawa
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
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Okano
Department of Physiology, Keio University School of Medicine, Tokyo, Japan Department of Cancer Biology, Faculty of Medicine, Shimane University, Shimane, Japan matsuzak@med.shimane-u.ac.jp.
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Matsuzaki
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001847:Bone Diseases / Q000601:surgery; D001861:Bone Regeneration / Q000502:physiology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003470:Culture Media; D003782:Dental Pulp / Q000166:cytology*; D005347:Fibroblasts / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009419:Nerve Tissue Proteins / Q000032:analysis; D010012:Osteogenesis / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D018800:Thy-1 Antigens / Q000032:analysis; D055815:Young Adult
D015703:Antigens, CD; D003470:Culture Media; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D018800:Thy-1 Antigens
THY-1; bone regeneration; flow cytometry; isolation; low-affinity nerve growth factor receptor; transplantation