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

Abstract

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.

Functional Dental Pulp Regeneration: Basic Research and Clinical Translation

“…Undoubtedly, pulp revascularisation has significantly improved treatment strategies, providing a minimally invasive approach and infection control; however, it still has some complications and limitations (Table 1) [21][22][23]. Although it has been used clinically, pulp revascularisation cannot be referred to as pulp regeneration.…”

“…Much effort has been made to improve clinical efficacy, such as adding platelet-rich plasma (PRP), platelet-derived growth factor (PDGF) and other active factors [25]. Undoubtedly, pulp revascularisation has significantly improved treatment strategies, providing a minimally invasive approach and infection control; however, it still has some complications and limitations (Table 1) [21][22][23]. Although it has been used clinically, pulp revascularisation cannot be referred to as pulp regeneration.…”

“…Stem cells are integral parts of modern tissue engineering aimed at regeneration, especially when the damage is too extensive to self-regenerate or taking cell-free approaches. Cell based-pulp regeneration is similar to the general understanding of tissue engineering concepts that adopts cell-based therapies, and requires a cell source delivered into the host for tissue to regenerate to its original or close to its original state [22]. Various application strategies of stem cells are promising to regenerate a pulpodentinal complex and to promote the translation of laboratory experiments into clinical applications.…”

Mesenchymal Stem Cells Based Treatment in Dental Medicine: A Narrative Review

“…There have been attempts to explore regenerative treatments and apply MSCs with the purpose of regenerating the pulp but with limited success. The obstacles faced in such procedures are high treatment costs, bacterial contamination of the internal tooth anatomy, and unpredictability of the treatment [4,5].…”

Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics

“…Regenerative endodontics (RE) has been defined as “biologically-based procedures designed to physiologically replace damaged tooth structures, including dentin and root structures, as well as cells of the pulp–dentin complex”[ 1 ]. The goal of RE is the restoration of the natural function of the dental pulp, including sensing exogenous stimuli, activating defense reactions, and forming reparative dentin, which contributes to the long-term preservation of natural teeth and dentition.…”