Effects of Growth Factors on Cellular Activities of Dental Stem Cells: A Systematic Review and Meta-analysis (Part I)

To evaluate the biological interaction between dental stem cells (DSCs) and different growth factors in the field of regenerative endodontics.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.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 (P0.05) and on ALP activity on days 5 and 7 (P0.05). 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 (P0.05).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.