Investigation of multipotent postnatal stem cells from human periodontal ligament.
BACKGROUND
Periodontal diseases that lead to the destruction of periodontal tissues--including periodontal ligament (PDL), cementum, and bone--are a major cause of tooth loss in adults and are a substantial public-health burden worldwide. PDL is a specialised connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. We investigated the notion that human PDL contains stem cells that could be used to regenerate periodontal tissue.


METHODS
PDL tissue was obtained from 25 surgically extracted human third molars and used to isolate PDL stem cells (PDLSCs) by single-colony selection and magnetic activated cell sorting. Immunohistochemical staining, RT-PCR, and northern and western blot analyses were used to identify putative stem-cell markers. Human PDLSCs were transplanted into immunocompromised mice (n=12) and rats (n=6) to assess capacity for tissue regeneration and periodontal repair. Findings PDLSCs expressed the mesenchymal stem-cell markers STRO-1 and CD146/MUC18. Under defined culture conditions, PDLSCs differentiated into cementoblast-like cells, adipocytes, and collagen-forming cells. When transplanted into immunocompromised rodents, PDLSCs showed the capacity to generate a cementum/PDL-like structure and contribute to periodontal tissue repair.


CONCLUSIONS
Our findings suggest that PDL contains stem cells that have the potential to generate cementum/PDL-like tissue in vivo. Transplantation of these cells, which can be obtained from an easily accessible tissue resource and expanded ex vivo, might hold promise as a therapeutic approach for reconstruction of tissues destroyed by periodontal diseases.
Seo
Byoung-Moo
BM
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Miura
Masako
M
Gronthos
Stan
S
Bartold
Peter Mark
PM
Batouli
Sara
S
Brahim
Jaime
J
Young
Marian
M
Robey
Pamela Gehron
PG
Wang
Cun-Yu
CY
Shi
Songtao
S
D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003114:Colony-Forming Units Assay; D003739:Dental Cementum / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology; D010510:Periodontal Diseases / Q000628:therapy; D010513:Periodontal Ligament / Q000166:cytology*; D051381:Rats; D012038:Regeneration; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000032:analysis
D000954:Antigens, Surface; D051792:Basic Helix-Loop-Helix Proteins; D003094:Collagen; D014157:Transcription Factors; C093504:SCX protein, human; C503815:Scx protein, mouse; C503819:Scx protein, rat