Animal Models for Stem Cell-Based Pulp Regeneration

Foundation for Human Clinical Applications

Misako Nakashima, Koichiro Iohara, Marco C. Bottino, Ashraf F. Fouad, Jacques E. Nör, George Huang

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Rapid progress has been made in the last decade related to stem cell-mediated pulp-dentin regeneration, from characterization of dental pulp stem cells (DPSCs) to the first-ever reported clinical case in humans. However, many challenges still need to be addressed before such technology can become a common clinical practice; therefore, further rigorous research is needed. Animal study models are very important to test new ideas, concepts, and technologies. This review summarizes and discusses several key animal models that have been utilized to investigate pulp-dentin regeneration. From a tissue regeneration perspective, we categorize the animal model by the location where the regenerated pulp tissue is formed: ectopic, semiorthotopic, and orthotopic. Several animal species are discussed, including mouse, ferret, dog, and miniswine. Mouse is used for ectopic pulp-dentin regeneration in the dorsum subcutaneous space. A commonly tested approach is hydroxyapatite/tricalcium phosphate (HA-TCP) granules model used to observe ectopic pulp-dentin complex formation. The semiorthotopic model includes tooth slices or fragments with which de novo pulp regeneration in a root canal space can be tested in the mouse subcutaneous space. For orthotopic pulp regeneration, the canine teeth of ferrets are large enough for such purposes. As nonprimate large animal models, dog and miniswine teeth have many aspects quite similar to those of humans, allowing researchers to perform experiments that mimic clinical conditions in humans. The protocols established and the data obtained from large animal studies may directly relate to and apply to future human studies. Complete orthotopic pulp regeneration has been demonstrated in dogs and miniswine. The use of allogeneic and subpopulations of DPSCs for pulp regeneration, and testing of the periapical disease model and aging model have been performed in miniswine or dogs. In sum, all these animal models will help address challenges that still face pulp regeneration in humans. We need to thoroughly utilize these models to test new ideas, technologies, and strategies before reliable and predictable clinical protocols can be established for human clinical trials or treatment. Animal models are essential for tissue regeneration studies. This review summarizes and discusses the small and large animal models, including mouse, ferret, dog, and miniswine that have been utilized to experiment and to demonstrate stem cell-mediated dental pulp tissue regeneration. We describe the models based on the location where the tissue regeneration is tested - either ectopic, semiorthotopic, or orthotopic. Developing and utilizing optimal animal models for both mechanistic and translational studies of pulp regeneration are of critical importance to advance this field.

Original languageEnglish (US)
Pages (from-to)100-113
Number of pages14
JournalTissue Engineering - Part B: Reviews
Volume25
Issue number2
DOIs
StatePublished - Apr 1 2019

Fingerprint

Stem cells
Pulp
Regeneration
Animals
Stem Cells
Animal Models
Tissue regeneration
Dentin
Dental Pulp
Ferrets
Dogs
Technology
Periapical Diseases
Tooth
Cuspid
Dental Pulp Cavity
Durapatite
Clinical Protocols
Canals
Hydroxyapatite

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

Cite this

Animal Models for Stem Cell-Based Pulp Regeneration : Foundation for Human Clinical Applications. / Nakashima, Misako; Iohara, Koichiro; Bottino, Marco C.; Fouad, Ashraf F.; Nör, Jacques E.; Huang, George.

In: Tissue Engineering - Part B: Reviews, Vol. 25, No. 2, 01.04.2019, p. 100-113.

Research output: Contribution to journalReview article

Nakashima, Misako ; Iohara, Koichiro ; Bottino, Marco C. ; Fouad, Ashraf F. ; Nör, Jacques E. ; Huang, George. / Animal Models for Stem Cell-Based Pulp Regeneration : Foundation for Human Clinical Applications. In: Tissue Engineering - Part B: Reviews. 2019 ; Vol. 25, No. 2. pp. 100-113.
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