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Regeneration of pulp-dentin complex using human stem cells of the apical papilla: in vivo interaction with two bioactive materials

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Abstract

Objectives

To compare the regenerative properties of human stem cells of the apical papilla (SCAPs) embedded in a platelet-rich plasma (PRP) scaffold, when implanted in vivo using an organotypic model composed of human root segments, with or without the presence of the bioactive cements – ProRoot MTA or Biodentine.

Material and methods

SCAPs were isolated from third molars with incomplete rhizogenesis and expanded and characterized in vitro using stem cell and surface markers. The pluripotency of these cells was also assessed using adipogenic, chondrogenic, and osteogenic differentiation protocols. SCAPs together with a scaffold of PRP were added to the root segment lumen and the organotypic model implanted on the dorsal region of immunodeficient rats for a period of 4 months.

Results

Presence of SCAPs induced de novo formation of dentin-like and pulp-like tissue. A barrier of either ProRoot MTA or Biodentine did not significantly affect the fraction of sections from roots segments observed to contain deposition of hard material (P > 0.05). However, the area of newly deposited dentin was significantly greater in segments containing a barrier of Biodentine compared with ProRoot MTA (P < 0.001).

Conclusions and clinical relevance

SCAPs offer a viable alternative to other dental stem cells (DSCs) in their regenerative properties when enclosed in the microenvironment of human tooth roots. The present study also suggests that the presence of bioactive materials does not hinder or impede the formation of new hard tissues, but the presence of Biodentine may promote greater mineralized tissue deposition.

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Acknowledgments

The authors thank Cláudia Brites, dedicated technician of the Hard Tissues Histology Laboratory, Faculty of Medicine, University of Coimbra, for assisting with the histological processing and staining. This project received funding from GAI, Gabinete Apoio à Investigação, Faculty of Medicine, University of Coimbra and the European Union’s Horizon 2020 research and innovation programme under grant agreement Number 799164. This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 and through the COMPETE 2020 - OperationalProgramme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, under project UIDB/04539/2020.

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Authors and Affiliations

  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Diana B. Sequeira, Ana Rafaela Oliveira, Catarina M. Seabra, Ana L. Cardoso & João Peça

  2. Institute of Endodontics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Diana B. Sequeira, Paulo J. Palma, Maria H. Figueiredo & João Miguel Santos

  3. MIT Portugal PhD Program, Universidade Nova de Lisboa, Lisbon, Portugal

    Ana Rafaela Oliveira

  4. Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal

    Catarina M. Seabra, Ana L. Cardoso & João Miguel Santos

  5. Coimbra Institute for Clinical and Biomedical Research (iCBR) – CIBB, University of Coimbra, Coimbra, Portugal

    Carlos Ramos & Ana C. Santos

  6. Institute of Biophysics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Carlos Ramos & Ana C. Santos

  7. Department of Life Sciences, University of Coimbra, Coimbra, Portugal

    João Peça

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  1. Diana B. Sequeira
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Correspondence to João Miguel Santos.

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The procedures and study protocol described here were approved by the Ethics Committee of the Faculty of Medicine, University of Coimbra (Project CE-028/2016) and following the guidelines of the Declaration of Helsinki.

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Sequeira, D.B., Oliveira, A.R., Seabra, C.M. et al. Regeneration of pulp-dentin complex using human stem cells of the apical papilla: in vivo interaction with two bioactive materials. Clin Oral Invest 25, 5317–5329 (2021). https://doi.org/10.1007/s00784-021-03840-9

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