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

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.