Effects of Growth Factors on the Differentiation of Dental Stem Cells: A Systematic Review and Meta-analysis

Abstract

Introduction: To evaluate the biological interaction between dental stem cells (DSCs) and different growth factors in the field of regenerative endodontics. Methods: A systematic search was conducted in the electronic databases up to October 2021. This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Ex vivo studies evaluating the biological interactions of DSCs and growth factors were included. The meta-analysis was performed according to the type of growth factor. The outcomes were cell viability/proliferation and mineralization. Standardized mean differences (SMDs) were estimated using the random-effect maximum-likelihood method (P<.05). Additional analysis was performed to find any potential source of heterogeneity. Results: Twenty articles were included in the systematic review; meta-analysis was performed for fibroblast growth factor-2 (FGF-2) and Transforming growth factor-ß1 (TGF-ß1) (n=5). Results showed that use of FGF-2 significantly increased cell proliferation on day 1-(SMD=3.56,P=0.00), 3-(SMD=9.04,P=0.00), 5-(SMD=8.37,P=0.01), and 7 (SMD=8.51,P=0.00) than the control group. TGF-ß1 increased alkaline phosphatase (ALP) activity more than control only on day 3 (SMD=3.68,P=0.02). TGF-ß1 had no significant effect on cell proliferation on days 1 and 3 (P>0.05) and on ALP activity on days 5 and 7 (P>0.05). Meta-regression analysis showed that different covariates (i.e., cell type, passage number, and growth factors' concentration) could significantly influence the effect sizes at different follow-ups (P<0.05). Conclusion: Specific growth factors might enhance the proliferation and mineralization of DSCs; however, the obtained evidence was weak. Due to the high heterogeneity among the included studies, other growth factors' inhibitory/stimulatory effects on DSCs could not be evaluated.