A new direction in managing avulsed teeth: stem cell-based de novo PDL regeneration

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Abstract

Management of avulsed teeth after replantation often leads to an unfavorable outcome. Damage to the thin and vulnerable periodontal ligament is the key reason for failure. Cell- or stem cell-based regenerative medicine has emerged in the past two decades as a promising clinical treatment modality to improve treatment outcomes. This concept has also been tested for the management of avulsed teeth in animal models. This review focuses on the discussion of limitation of current management protocols for avulsed teeth, cell-based therapy for periodontal ligament (PDL) regeneration in small and large animals, the challenges of de novo regeneration of PDL on denuded root in the edentulous region using a mini-swine model, and establishing a prospective new clinical protocol to manage avulsed teeth based on the current progress of cell-based PDL regeneration studies.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13287-022-02700-x.

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Most cited references 85

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Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

S Gronthos, M Mankani, J Brahim … (2000)

Dentinal repair in the postnatal organism occurs through the activity of specialized cells, odontoblasts, that are thought to be maintained by an as yet undefined precursor population associated with pulp tissue. In this study, we isolated a clonogenic, rapidly proliferative population of cells from adult human dental pulp. These DPSCs were then compared with human bone marrow stromal cells (BMSCs), known precursors of osteoblasts. Although they share a similar immunophenotype in vitro, functional studies showed that DPSCs produced only sporadic, but densely calcified nodules, and did not form adipocytes, whereas BMSCs routinely calcified throughout the adherent cell layer with clusters of lipid-laden adipocytes. When DPSCs were transplanted into immunocompromised mice, they generated a dentin-like structure lined with human odontoblast-like cells that surrounded a pulp-like interstitial tissue. In contrast, BMSCs formed lamellar bone containing osteocytes and surface-lining osteoblasts, surrounding a fibrous vascular tissue with active hematopoiesis and adipocytes. This study isolates postnatal human DPSCs that have the ability to form a dentin/pulp-like complex.

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Investigation of multipotent postnatal stem cells from human periodontal ligament.

Byoung-Moo Seo, Masako Miura, Stan Gronthos … (2004)

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. 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. 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.

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Dynamics of bone tissue formation in tooth extraction sites. An experimental study in dogs.

G Cardaropoli, M. Araujo, J Lindhe (2003)

The aim of the present experiment was to study events involved in the healing of marginal, central and apical compartments of an extraction socket, from the formation of a blood clot, to bone tissue formation and remodeling of the newly formed hard tissue. Nine mongrel dogs were used for the experiment. The fourth mandibular premolars were selected for study and were divided into one mesial and one distal portion. The distal root was removed and the socket with surrounding soft and mineralized tissue was denoted "experimental unit". The dogs were killed 1, 3, 7, 14, 30, 60, 90, 120 and 180 days after the root extractions. Biopsies including the experimental units were demineralized in EDTA, dehydrated in ethanol and embedded in paraffin. Serial sections 7 microm thick were cut in a mesio-distal plane. From each biopsy, three sections representing the central part of the socket were selected for histological examination. Morphometric measurements were performed to determine the volume occupied by different types of tissues in the marginal, central and apical compartments of the extraction socket at different intervals. During the first 3 days of healing, a blood clot was found to occupy most of the extraction site. After seven days this clot was in part replaced with a provisional matrix (PCT). On day 14, the tissue of the socket was comprised of PM and woven bone. On day 30, mineralized bone occupied 88% of the socket volume. This tissue had decreased to 15% on day 180. The portion occupied by bone marrow (BM) in the day 60 specimens was about 75%, but had increased to 85% on day 180. The healing of an extraction socket involved a series of events including the formation of a coagulum that was replaced by (i) a provisional connective tissue matrix, (ii) woven bone, and (iii) lamellar bone and BM. During the healing process a hard tissue bridge--cortical bone--formed, which "closed" the socket.

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Author and article information

Contributors

George T.-J. Huang:

ORCID: http://orcid.org/0000-0001-9822-8748

gtjhuang@uthsc.edu

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 28 January 2022

Publication date PMC-release: 28 January 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 34

Affiliations

[1 ]GRID grid.267301.1, ISNI 0000 0004 0386 9246, Department of Bioscience Research, College of Dentistry, , University of Tennessee Health Science Center, ; Memphis, TN USA

[2 ]GRID grid.273335.3, ISNI 0000 0004 1936 9887, Department of Periodontics and Endodontics, , School of Dental Medicine, University at Buffalo, ; Buffalo, USA

[3 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Endodontics, Henry M. Goldman School of Dental Medicine, , Boston University, ; Boston, MA USA

[4 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, VIP Dental Service and Geriatric Dentistry, , Peking University School and Hospital of Stomatology, ; Beijing, China

[5 ]GRID grid.23856.3a, ISNI 0000 0004 1936 8390, Département d’endodontie, Faculté de Médecine Dentaire, , Université Laval, ; Québec, QC G1V 0A6 Canada

[6 ]GRID grid.267301.1, ISNI 0000 0004 0386 9246, Department of Genetics, Genomics and Informatics, College of Medicine, , University of Tennessee Health Science Center, ; Memphis, USA

[7 ]GRID grid.254662.1, ISNI 0000 0001 2152 7491, Department of Endodontics, Arthur A Dugoni School of Dental Medicine, , University of Pacific, ; San Francisco, California USA

[8 ]GRID grid.267301.1, ISNI 0000 0004 0386 9246, Cancer Research Building, , University of Tennessee Health Science Center, ; 19 S. Manassas St. Lab Rm 256, office 255, Memphis, TN 38163 USA

Author information

George T.-J. Huang http://orcid.org/0000-0001-9822-8748

Article

Publisher ID: 2700

DOI: 10.1186/s13287-022-02700-x

PMC ID: 8796335

PubMed ID: 35090556

SO-VID: d7cbc7c3-966c-4d7c-9bc7-f7e4faa04c23

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 1 June 2021

Date accepted : 16 November 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000072, National Institute of Dental and Craniofacial Research;

Award ID: R01 DE019156

Award Recipient : George T.-J. Huang

Funded by: FundRef http://dx.doi.org/10.13039/100002569, American Association of Endodontists Foundation;

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: avulsion,traumatic injury,periodontal ligament (pdl),periodontal ligament stem cells (pdlscs),cell-based pdl regeneration,cell sheet,tooth replantation,animal models,mini-swine,dog

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: avulsion, traumatic injury, periodontal ligament (pdl), periodontal ligament stem cells (pdlscs), cell-based pdl regeneration, cell sheet, tooth replantation, animal models, mini-swine, dog

A new direction in managing avulsed teeth: stem cell-based de novo PDL regeneration

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Abstract

Supplementary Information

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Most cited references 85

Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

Investigation of multipotent postnatal stem cells from human periodontal ligament.

Dynamics of bone tissue formation in tooth extraction sites. An experimental study in dogs.

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