Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications

Nakashima, Mitsuyoshi; Iohara, Koichiro; Bottino, Marco C.; Fouad, Ashraf F.; Huang, George T.‐J.

doi:10.1089/ten.teb.2018.0194

Cited by 54 publications

(48 citation statements)

References 78 publications

(116 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though CB‐RET has yet to reach clinical practice and with only limited clinical trials being reported, extensive studies using animal models have been conducted and reported (Nakashima et al . 2019). The key differences between CF‐RET and CB‐RET being the scaffolds that are introduced, stem cells and growth factors, which are elaborated in Fig 3.…”

Section: Cb‐retsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

et al. 2021

View full text Add to dashboard Cite

There is no consensus on the true meaning of clinical regenerative endodontics, and there is confusion over the concept and the term. Commonly used terms include revitalization and revascularization. The clinical methods for endodontic revitalization procedures and the tissue engineering concept differ depending on whether there is exogenous delivery of cells – called cell therapy, or not. Here, in this review, the difference is clarified by emphasizing the correct terminology: cell‐free versus cell‐based regenerative endodontic therapy (CF‐RET versus CB‐RET). The revitalization procedures practised clinically do not fit into the modern tissue engineering concepts of pulp regeneration but can be categorized as CF‐RET. The modern tissue engineering concept in pulp regeneration is a CB‐RET, which so far is at the clinical trial stage. However, histological examination of teeth following regenerative endodontic treatments reveals healing with repair derived from stem cells that originate from the periodontal, bone and other tissues. The aim of regenerative endodontics is regeneration of the pulp–dentine complex. This review discusses why CF‐RET is unlikely to regenerate a pulp–dentine complex with current protocols. The American Association of Endodontists and the European Society of Endodontology have not yet recommended autologous stem cell transplantation (CB‐RERT) which aspires for regeneration. Therefore, an understanding of the concept, term, difficulties and differences in current protocols is important for the clinician. However, rather than being discouraged that ideal regeneration has not been achieved to date, repair can be an acceptable outcome in clinical regenerative endodontics as it has also been accepted in medicine. Repair should also be considered in the context that resolution of the clinical signs/symptoms of pulp necrosis/apical periodontitis is generally reliably obtained in clinical regenerative endodontics.

show abstract

Section: Cb‐retsmentioning

confidence: 99%

“…For a review, see Nakashima et al . (2019). The control group where no stem cells were introduced had no pulp regeneration.…”

Section: Cb‐retsmentioning

confidence: 99%

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Miniature swine have been identified as a suitable animal biomedical model with the advantages of physiological, genetic, and anatomical similarities to humans 45 , 46 . In the dental regenerative field, minipig models have been utilized for various in vivo studies on pulp-dentin regeneration 46 – 48 , vital pulp therapy 49 , 50 , and periodontal bone tissue regeneration 51 , 52 . In this study, we used extirpated immature premolars of minipigs as a RET model to evaluate radiographic and histologic results over time.…”

Section: Discussionmentioning

confidence: 99%

Pulp regeneration with hemostatic matrices as a scaffold in an immature tooth minipig model

Jang

Moon

Kim

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Control of blood clotting in root canal systems is one of the most critical and difficult concerns for regenerative endodontics therapy (RET). The purpose of this study was to investigate the effects of using gelatin- and fibrin-based hemostatic hydrogels as a scaffold on pulp regeneration in a minipig model . Cell viability of human dental pulp stem cells cultured three-dimensionally in gelatin-based and fibrin-based scaffolds was evaluated by MTT and live/dead assay. RET was performed on 24 immature premolars with an autologous blood clot (PC), gelatin-based and fibrin-based hemostatic matrices (GM and FM), or without the insertion of a scaffold (NC). The follow-up period was 12 weeks. Radiographic and histologic assessments for pulp regeneration were performed. Gelatin-based scaffolds exhibited significantly higher cell viability than fibrin-based scaffolds after 15 days ( P < 0.05). The PC and GM groups showed favorable root development without inflammation and newly mineralized tissue deposited in the root canal system, while FM group presented inflammatory changes with the continuation of root development. The NC group exhibited internal root resorption with periapical lesions. The application of GM in RET led to favorable clinical outcomes of root development without inflammatory changes compared to conventional RET. Our results suggest that GM may serve as a viable regenerative scaffold for pulp regeneration.

show abstract

“…TE of various dental tissues, through cell-based 23 or cell-free approaches 24 , has been accomplished. Sophisticated in vitro and in vivo systems have been developed 25 . Bioengineering of various constituents of dental tissues, such as dentin 26,27 , pulp [28][29][30] , enamel 31,32 , periodontal tissues 33 , or alveolar bone 34,35 , has been achieved by the combination of scaffolds, SCs, and growth factors (TE triad) 18 .…”

Section: Significancementioning

confidence: 99%

Prospects of Advanced Therapy Medicinal Products–Based Therapies in Regenerative Dentistry: Current Status, Comparison with Global Trends in Medicine, and Future Perspectives

Bakopoulou

2020

Journal of Endodontics

View full text Add to dashboard Cite

Introduction: Regenerative medicine offers innovative approaches to restore damaged tissues on the basis of tissue engineering (TE). Although research on advanced therapy medicinal products (ATMPs) has been very active in recent years, the number of licensed products remains surprisingly low and restricted to the treatment of severe, incurable diseases. Methods: This paper provides a critical review of current literature on the regulatory, clinical, and commercial status of ATMP-based therapies in the EU and worldwide and the hurdles to overcome for their broader application in Regenerative Dentistry. Results: Competent authorities have focused on developing regulatory pathways to address unmet patient needs. Oncology represents the dominating field, followed by cardiovascular, musculoskeletal, neurodegenerative, immunologic, and inherited diseases. Yet, the status remains in early development, and scientific, regulatory, and cost-effectiveness issues impose considerable hurdles toward marketing authorization, technology adoption, and patient accessibility. In this context, although regenerative dentistry has achieved breakthrough innovations in TE of several dental/oral tissues in preclinical models, it has hardly harnessed research progress to integrate innovative regenerative treatments into clinical practice. Conclusion: Global demographic changes, which demonstrate a steady increase of the aging population, highlight the societal need for the application of ATMP-based therapies in the treatment of noncommunicable diseases (NCDs). Although oral diseases, as an integral part of NCDs, are not life-threatening and largely preventable, they sustain high prevalence, with severe burden on economy and quality of life. In this perspective, the urgent request to ultimately translate draining research in dental TE conducted during the last decades into innovative treatments brought safely and cost-effectively into society at large still holds the stage. This review provides an overview of the regulatory, clinical, and commercial status of ATMP-based therapies in the European Union and worldwide and the hurdles to overcome for their broader application in regenerative dentistry.

show abstract

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications

Cited by 54 publications

References 78 publications

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term

Pulp regeneration with hemostatic matrices as a scaffold in an immature tooth minipig model

Prospects of Advanced Therapy Medicinal Products–Based Therapies in Regenerative Dentistry: Current Status, Comparison with Global Trends in Medicine, and Future Perspectives

Contact Info

Product

Resources

About