title: Investigation of dental pulp stem cells isolated from discarded human teeth extracted due to aggressive periodontitis.
abstract: Recently, human dental pulp stem cells (DPSCs) isolated from inflamed dental pulp tissue have been demonstrated to retain some of their pluripotency and regenerative potential. However, the effects of periodontal inflammation due to periodontitis and its progression on the properties of DPSCs within periodontally compromised teeth remain unknown. In this study, DPSCs were isolated from discarded human teeth that were extracted due to aggressive periodontitis (AgP) and divided into three experimental groups (Groups A, B and C) based on the degree of inflammation-induced bone resorption approaching the apex of the tooth root before tooth extraction. DPSCs derived from impacted or non-functional third molars of matched patients were used as a control. Mesenchymal stem cell (MSC)-like characteristics, including colony-forming ability, proliferation, cell cycle, cell surface antigens, multi-lineage differentiation capability and in vivo tissue regeneration potential, were all evaluated in a patient-matched comparison. It was found that STRO-1- and CD146-positive DPSCs can be isolated from human teeth, even in very severe cases of AgP. Periodontal inflammation and its progression had an obvious impact on the characteristics of DPSCs isolated from periodontally affected teeth. Although all the isolated DPSCs in Groups A, B and C showed decreased colony-forming ability and proliferation rate (P < 0.05), the decreases were not consistent with the degree of periodontitis. Furthermore, the cells did not necessarily show significantly diminished in vitro multi-differentiation potential. Only DPSCs from Group A and the Control group formed dentin-like matrix in vivo when cell-seeded biomaterials were transplanted directly into an ectopic transplantation model. However, when cell-seeded scaffolds were placed in the root fragments of human teeth, all the cells formed significant dentin- and pulp-like tissues. The ability of DPSCs to generate dental tissues decreased when the cells were isolated from periodontally compromised teeth (P < 0.05). Again, increased periodontal destruction was not necessarily followed by a decrease in the amount of dentin- and pulp-like tissue formed. These findings provide preliminary evidence that periodontally compromised teeth might contain putative stem cells with certain MSC properties, as long as the vitality of the pulp has not been totally damaged. Whether these cells can serve as a source of autologous multipotent MSCs for clinical regenerative therapies warrants further investigation with larger sample sizes and various types of periodontitis.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China; State Key Laboratory of Military Stomatology, Translational Research Team, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Qing-Lin
authors.initials: QL
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Stomatology, Affiliated Hospital of Academy of Military Medical Science, Beijing, PR China.
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Translational Research Team, School of Stomatology, Fourth Military Medical University, Xi'an, PR China; State Key Laboratory of Military Stomatology, Department of Periodontology & Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Military Stomatology, Translational Research Team, School of Stomatology, Fourth Military Medical University, Xi'an, PR China; State Key Laboratory of Military Stomatology, Department of Periodontology & Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, PR China. Electronic address: cfmsunhh@fmmu.edu.cn.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, PR China; State Key Laboratory of Military Stomatology, Translational Research Team, School of Stomatology, Fourth Military Medical University, Xi'an, PR China. Electronic address: yuqing@fmmu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000328:Adult; D010520:Aggressive Periodontitis / Q000628:therapy*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003114:Colony-Forming Units Assay / Q000379:methods; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D003804:Dentin / Q000166:cytology / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry; D014092:Tooth Root / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials
keywords: Aggressive periodontitis; Dental pulp stem cells; Inflamed dental pulp; Periodontal inflammation; Stem cell therapy; Tissue engineering