All-Trans Retinoic-Acid (ATRA) Effects on Dental Pulp-Derived Stem Cells (DPSC)

Objectives: Dental Pulp-Derived Stem Cells (DPSC) are multipotent mesenchymal stem cells, which maintain significant capacity for self-renewal. Recent studies have focused on the potential to differentiate DPSC into functional cell types, including neuronal precursors – which may help in the development of treatments for neurological diseases including Parkinson’s and Alzheimer’s disease. Recent work from this group demonstrated all-trans retinoic acid (ATRA) administration was sufficient to alter DPSC growth and induce changes to cellular morphology that suggested potential neuronal differentiation. The main objective of this study was to expand the number of DPSC isolates tested and to determine the molecular changes associated with these observations.

Methods: Using previously isolated and characterized DPSC isolates, ATRA was administrated within a previously established physiologically relevant range of 1-20 uL/mL on four DPSC isolates (dpsc-11750, -11418, -5653, -3921). RNA was isolated for mRNA screening using RT-PCR.

Results: ATRA induced significant and similar reductions in cellular growth in all four DPSC isolates (range -30.4% to -45.8%), suggesting changes to doubling time indicative of partial cellular differentiation. Analysis of mRNA using RT-PCR suggested strong reductions in biomarkers associated with DPSC, including CD24, Oct4 and p27 – another indication these DPSC may be experiencing partial differentiation and loss of “stem-ness”.

Conclusions: This study may be among the first to demonstrate that ATRA may have the potential to induce phenotypic changes to DPSC in vitro that suggest phenotypic, behavioral and biochemical alterations associated with cellular differentiation. Evaluation of biomarkers associated with neuronal differentiation are now currently underway. These studies may significantly enhance our understanding of potential methods and pathways associated with DPSC differentiation and the potential for DPSC-specific future treatments and therapies.