Stem/progenitor cell-mediated pulpal tissue regeneration: a systematic review and meta-analysis

Background Stem/progenitor cell-mediated pulpal regeneration could represent a promising therapeutic alternative in the field of clinical endodontics. Aim The present study aimed to systematically assess and meta-analyse dental pulpal tissue regeneration, pulpal vitality and apical healing after the transplantation of stem/progenitor cells versus no transplantation. Data sources MEDLINE, Cochrane CENTRAL and EMBASE were searched up to January 2019 for animal experiments and human trials evaluating the pulpal transplantation of stem/progenitor cells. Cross-referencing and hand search were additionally performed. Study eligibility criteria, participants and interventions Based on randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs), conducted in animals or humans, the effect of the transplantation of stem/progenitor cells compared to no transplantation on pulpal tissue regeneration, pulpal vitality and apical healing was examined. Study appraisal and synthesis methods The primary outcome was histologically determined pulpal tissue regeneration, whilst pulpal vitality and apical healing were secondary outcomes. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) guidelines and the revised Cochrane risk of bias tool (RoB 2.0) were used for risk-of-bias assessment. Pooled standardized differences in means (SDM) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analyses. Results From 2834 identified articles, eight animal experiments (82 animals with 336 experimental pulpal defects) and one human trial (40 humans with 40 pulpal defects) were included. Risk of bias of most animal studies was high, whilst the human trial revealed 'some concerns'. Stem/progenitor cell-transplanted pulps demonstrated significantly increased pulpal tissue regeneration compared with controls (SDM [95%CI]: 6.29 [3.78-8.80]). Limitations Data on pulpal vitality and apical healing were sparse and inconsistent. Heterogeneity across studies was substantial, publication bias was present, and mainly indirect, surrogate outcome measures were applied. The overall strength of evidence was very low. Conclusions and implications of key findings The transplanation of stem/progenitor cells shows promise for pulp regeneration, whilst clinical routine application is still not in reach. Further investigations, employing a comprehensive set of outcomes including those demonstrating functional pulp regeneration relevant for patient-centred care, are required.