Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

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Abstract

Human pulp stem cells (PSCs) include dental pulp stem cells (DPSCs) isolated from dental pulp tissues of human extracted permanent teeth and stem cells from human exfoliated deciduous teeth (SHED). Depending on their multipotency and sensitivity to local paracrine activity, DPSCs and SHED exert therapeutic applications at multiple levels beyond the scope of the stomatognathic system. This review is specifically concentrated on PSC‐updated biological characteristics and their promising therapeutic applications in (pre)clinical practice. Biologically, distinguished from conventional mesenchymal stem cell markers in vitro, NG2, Gli1, and Celsr1 have been evidenced as PSC markers in vivo . Both perivascular cells and glial cells account for PSC origin. Therapeutically, endodontic regeneration is where PSCs hold the most promises, attributable of PSCs' robust angiogenic, neurogenic, and odontogenic capabilities. More recently, the interplay between cell homing and liberated growth factors from dentin matrix has endowed a novel approach for pulp‐dentin complex regeneration. In addition, PSC transplantation for extraoral tissue repair and regeneration has achieved immense progress, following their multipotential differentiation and paracrine mechanism. Accordingly, PSC banking is undergoing extensively with the intent of advancing tissue engineering, disease remodeling, and (pre)clinical treatments.

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Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues.

Agnes Arthur, Grigori Y Rychkov, Songtao Shi … (2008)

Human adult dental pulp stem cells (DPSCs) reside within the perivascular niche of dental pulp and are thought to originate from migrating cranial neural crest (CNC) cells. During embryonic development, CNC cells differentiate into a wide variety of cell types, including neurons of the peripheral nervous system. Previously, we have demonstrated that DPSCs derived from adult human third molar teeth differentiate into cell types reminiscent of CNC embryonic ontology. We hypothesized that DPSCs exposed to the appropriate environmental cues would differentiate into functionally active neurons. The data demonstrated that ex vivo-expanded human adult DPSCs responded to neuronal inductive conditions both in vitro and in vivo. Human adult DPSCs, but not human foreskin fibroblasts (HFFs), acquired a neuronal morphology, and expressed neuronal-specific markers at both the gene and protein levels. Culture-expanded DPSCs also exhibited the capacity to produce a sodium current consistent with functional neuronal cells when exposed to neuronal inductive media. Furthermore, the response of human DPSCs and HFFs to endogenous neuronal environmental cues was determined in vivo using an avian xenotransplantation assay. DPSCs expressed neuronal markers and acquired a neuronal morphology following transplantation into the mesencephalon of embryonic day-2 chicken embryo, whereas HFFs maintained a thin spindle fibroblastic morphology. We propose that adult human DPSCs provide a readily accessible source of exogenous stem/precursor cells that have the potential for use in cell-therapeutic paradigms to treat neurological disease.

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Glial origin of mesenchymal stem cells in a tooth model system.

Nina Kaukua, Maryam Shahidi, Chrysoula Konstantinidou … (2014)

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.

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Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.

Chang Lee, James Cook, Avital Mendelson … (2010)

A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold. In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-epsilon-caprolactone and hydroxyapatite. The entire articular surface of unilateral proximal humeral condyles of skeletally mature rabbits was surgically excised and replaced with bioscaffolds spatially infused with transforming growth factor beta3 (TGFbeta3)-adsorbed or TGFbeta3-free collagen hydrogel. Locomotion and weightbearing were assessed 1-2, 3-4, and 5-8 weeks after surgery. At 4 months, regenerated cartilage samples were retrieved from in vivo and assessed for surface fissure, thickness, density, chondrocyte numbers, collagen type II and aggrecan, and mechanical properties. Ten rabbits received TGFbeta3-infused bioscaffolds, ten received TGFbeta3-free bioscaffolds, and three rabbits underwent humeral-head excision without bioscaffold replacement. All animals in the TGFbeta3-delivery group fully resumed weightbearing and locomotion 3-4 weeks after surgery, more consistently than those in the TGFbeta3-free group. Defect-only rabbits limped at all times. 4 months after surgery, TGFbeta3-infused bioscaffolds were fully covered with hyaline cartilage in the articular surface. TGFbeta3-free bioscaffolds had only isolated cartilage formation, and no cartilage formation occurred in defect-only rabbits. TGFbeta3 delivery yielded uniformly distributed chondrocytes in a matrix with collagen type II and aggrecan and had significantly greater thickness (p=0.044) and density (p<0.0001) than did cartilage formed without TGFbeta3. Compressive and shear properties of TGFbeta3-mediated articular cartilage did not differ from those of native articular cartilage, and were significantly greater than those of cartilage formed without TGFbeta3. Regenerated cartilage was avascular and integrated with regenerated subchondral bone that had well defined blood vessels. TGFbeta3 delivery recruited roughly 130% more cells in the regenerated articular cartilage than did spontaneous cell migration without TGFbeta3. Our findings suggest that the entire articular surface of the synovial joint can regenerate without cell transplantation. Regeneration of complex tissues is probable by homing of endogenous cells, as exemplified by stratified avascular cartilage and vascularised bone. Whether cell homing acts as an adjunctive or alternative approach of cell delivery for regeneration of tissues with different organisational complexity warrants further investigation. New York State Stem Cell Science; US National Institutes of Health. Copyright 2010 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Jing Mao: maojing@hust.edu.cn

Yan Liu:

ORCID: https://orcid.org/0000-0002-8193-6729

orthoyan@bjmu.edu.cn

Journal

Journal ID (nlm-ta): Stem Cells Transl Med

Journal ID (iso-abbrev): Stem Cells Transl Med

Journal ID (doi): 10.1002/(ISSN)2157-6580

Journal ID (publisher-id): SCT3

Title: Stem Cells Translational Medicine

Publisher: John Wiley & Sons, Inc. (Hoboken, USA )

ISSN (Print): 2157-6564

ISSN (Electronic): 2157-6580

Publication date (Electronic): 14 January 2020

Publication date Collection: April 2020

Volume: 9

Issue: 4 ( doiID: 10.1002/sct3.v9.4 )

Pages: 445-464

Affiliations

[ ¹ ] Center of Stomatology, Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan People's Republic of China

[ ² ] Laboratory of Biomimetic Nanomaterials, Department of Orthodontics Peking University School and Hospital of Stomatology Beijing People's Republic of China

Author notes

[*] [* ] Correspondence

Jing Mao, DDS, PhD, Center of Stomatology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Hankou, Wuhan 430030, People's Republic of China.

Email: maojing@ 123456hust.edu.cn

Yan Liu, DDS, PhD, Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, No. 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, People's Republic of China.

Email: orthoyan@ 123456bjmu.edu.cn

Author information

Yan Liu https://orcid.org/0000-0002-8193-6729

Article

Publisher ID: SCT312658

DOI: 10.1002/sctm.19-0398

PMC ID: 7103623

PubMed ID: 31943813

SO-VID: 21b05f86-aa16-47fa-a09c-49107ca1232a

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 21 November 2019

Date accepted : 27 December 2019

Page count

Figures: 4, Tables: 3, Pages: 21, Words: 16295

Funding

Funded by: Key Project of Health Commission of Hubei Province

Award ID: WJ2019Z006

Funded by: Beijing Municipal Natural Science Foundation , open-funder-registry 10.13039/501100004826;

Award ID: L182005

Funded by: National Natural Science Foundations of China , open-funder-registry 10.13039/501100001809;

Award ID: 81871492

Award ID: 81571815

Custom metadata

source-schema-version-number 2.0

cover-date April 2020

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.8 mode:remove_FC converted:30.03.2020

Keywords: cell banking,cell homing,pulp stem cells,pulp‐dentin regeneration,tissue regeneration

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Keywords: cell banking, cell homing, pulp stem cells, pulp‐dentin regeneration, tissue regeneration

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

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Most cited references 120

Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues.

Glial origin of mesenchymal stem cells in a tooth model system.

Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.

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