Simvastatin Promotes Dental Pulp Stem Cell–induced Coronal Pulp Regeneration in Pulpotomized Teeth

Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells

“…Regarding mineralized matrix deposition, we observed that the activity of these cells was increased after 14 days, except for the group in which the cells were treated with 0.1 µM SV in continuous mode. The data obtained in the present study do not corroborate the findings of previous investigations carried out by Min et al 6 , Lee et al, 15 and Jia et al 22 , in which the authors demonstrated a greater formation of mineralized matrix in human pulp cells exposed to 1 µM SV in continuous mode for 14 days. Okamoto et al 14 also related an enhancement in mineralized tissue formation when hDSPCs cells were treated with 0.1 µM SV in continuous mode for 7 days, and then transplanted into subcutaneous tissue of immunocompromised rats.…”

“…Exposure of MDPC-23 cells to 0.01 and 0.1 µM SV for 24 h, 72 h or in continuous mode caused no cytopathic effect at 1, 3 and 7 days, confirming the results obtained in previous laboratorial investigations, in which the authors used a primary culture of human pulp cells. 18,22,30 However, the treatment of cells with 0.1 µM SV at 72 h and in continuous mode decreased the cell proliferation at the later period; under these specific conditions, cell viability values were significantly lower than those of the NC at the 14-day period. Nevertheless, according to ISO 10993-5:2009 (E), the percentage of cell viability reduction mediated by SV in these groups may be considered slight, since it was less than 20%, compared with the NC.…”

“…Some researchers have found greater ALP activity in human pulp cells treated in continuous mode with SV, in the concentrations of 0.01, 0.1 µM 6,18 and 1 µM. 15,22 This increase in ALP activity observed in human pulp cells treated with SV seems to be related to the induction of odontogenic differentiation by activation of the ERK pathway. 18 SV is known to accelerate the expression of bone/dentin differentiation markers, such as ALP, OCN, OPN, Runx-2, Osterix, DSP and DMP-1, when applied to human dental pulp cells.…”

“…29 Moreover, some researchers have demonstrated a decrease in cell viability mediated by SV for other types of cells, such as smooth muscle cells, 31 neuronal cells, 32 bone marrow stem cells (BMSC), 33 adipose derivate mesenchymal stem cells (AD-MSC) 34 and hDSPCs cells. 22 Okamoto et al 14 reported that when SV concentrations higher than 1 µM were applied to hDSPCs cells, they inhibited the formation of actin fibers and interfered with progression of the cell cycle regulated by the Rho pathway. However, this reduction in cell proliferation was reestablished in the presence of mevalonate.…”

“…6,14,18 The positive effect of SV as a co-adjuvant in direct pulp capping has recently been assessed. 21,22 Although Asl Aminabadi et al (2013) 21 demonstrated that 1 μM SV caused deposition of a mineralized barrier on the exposed pulp tissue of primary human teeth, Jia et al 22 showed that this SV concentration was capable of inducing dentin regeneration after pulpotomy in dog teeth.…”