Immunomodulatory Effects of N-Acetyl Cysteine Treated SCAP

J Endod. 2022 Aug;48(8):1055-1062. doi: 10.1016/j.joen.2022.05.005. Epub 2022 May 17.

Abstract

Introduction: Stem cells of the apical papilla (SCAP) play an important role in regenerative endodontic procedures (REPs). Previous studies have shown that during REPs, bacteria can activate the innate immune system and cause indirect stem cell toxicity, leading to the lysis of SCAP. N-acetylcysteine (NAC)-treated cells are resistant to apoptosis and have increased differentiation capabilities. The immunomodulatory properties of NAC-treated SCAP are still unknown. Hence, the aim of this study is to evaluate the interactions of SCAP pretreated with and without NAC with the immune system.

Methods: Flow cytometric analysis was performed to assess the effects of NAC on SCAP viability. Human SCAP were then cultured and were either pretreated with NAC or non-treated and co-cultured with human peripheral blood mononuclear cells. A lactate dehydrogenase assay was performed to evaluate the levels of immune cell mediated apoptosis, followed by an enzyme-linked immunosorbent assay (ELISA) to measure levels of proinflammatory cytokines for these co-cultures. Data were analyzed using analysis of variance with post hoc Tukey test.

Results: Cells treated with NAC had similar levels of viability as the controls. SCAP pretreated with NAC had significantly lower immune cell-mediated cytotoxicity to nonactivated and activated peripheral blood mononuclear cells. The ELISA results showed that SCAP pretreated with NAC induced lower levels of proinflammatory cytokines.

Conclusions: SCAP pretreated with NAC have a higher chance of surviving the activated immune system. This information may provide a better insight into the properties of these stem cells and may be the key to making REPs more predictable.

Keywords: Cytokines; N-acetyl cysteine; SCAP; cytotoxicity; immune cells.

MeSH terms

  • Acetylcysteine* / pharmacology
  • Cell Differentiation
  • Cytokines
  • Dental Papilla
  • Humans
  • Leukocytes, Mononuclear*
  • Stem Cells

Substances

  • Cytokines
  • Acetylcysteine