IADR Abstract Archives
Impact of Benzo-lipoxin A4 (BLXA4) on Mesenchymal Stem Cells
Objectives: Mesenchymal Stem Cells (MSC) are defined by their ability to self-renew and differentiate into cells of mesodermal lineage. MSC play an important role in tissue regeneration, but it is their immunomodulatory, paracrine, and trophic functions at sites of inflammation and tissue damage that have the greatest therapeutic impact. Specialized Proresolving Mediators (SPMs) are a family of endogenous lipid mediators that include LXA4), which has been shown to promote periodontal regeneration. Active, receptor mediated, resolution of acute inflammation is at the interface between innate and adaptive immunity. In this study, we investigated the role of BLXA4 in regulating MSC proliferation and secretion of pro-inflammatory lipid mediators and resolution phase mediators.
Methods: Passage 4 human bone marrow-derived MSC were seeded at 6X103 cells/cm2 in a-MEM containing 7% FBS until 80% confluent and then treated with BLXA4 (0.1 nM) for 24 hours after 24 hours incubation in 1% FBS. Untreated cells served as control. Supernatants were collected, MSC were lysed in liquid nitrogen and Lipid Mediator Metabololipidomics was performed for lipid mediator profiles. In another experiment, MSC were treated with BLXA4 at concentrations of 0.01, 0.1, and 1.0 nM. MSC proliferation was assessed by cell counting after 24, 48, and 72 hours.
Results: MSC treated with BLXA4 showed an increase in LXA4 secretion (p < 0.05) and a marked decrease in the secretion of resolvin and maresin precursors compared to control that is reflected in an increase in RvD2 in the supernatants (P < 0.05). A statistically significant difference (p<0.05) in MSC proliferation was noted after 0.1 nM BLXA4 treatment at 72 hours.
Conclusions: BLXA4 treatment modulates SPM secretion by MSC and enhances MSC proliferation in vitro. The data suggest that stem cells respond positively to SPMs to reduce local inflammation and increase stem cell numbers providing an environment favorable for tissue regeneration.
Methods: Passage 4 human bone marrow-derived MSC were seeded at 6X103 cells/cm2 in a-MEM containing 7% FBS until 80% confluent and then treated with BLXA4 (0.1 nM) for 24 hours after 24 hours incubation in 1% FBS. Untreated cells served as control. Supernatants were collected, MSC were lysed in liquid nitrogen and Lipid Mediator Metabololipidomics was performed for lipid mediator profiles. In another experiment, MSC were treated with BLXA4 at concentrations of 0.01, 0.1, and 1.0 nM. MSC proliferation was assessed by cell counting after 24, 48, and 72 hours.
Results: MSC treated with BLXA4 showed an increase in LXA4 secretion (p < 0.05) and a marked decrease in the secretion of resolvin and maresin precursors compared to control that is reflected in an increase in RvD2 in the supernatants (P < 0.05). A statistically significant difference (p<0.05) in MSC proliferation was noted after 0.1 nM BLXA4 treatment at 72 hours.
Conclusions: BLXA4 treatment modulates SPM secretion by MSC and enhances MSC proliferation in vitro. The data suggest that stem cells respond positively to SPMs to reduce local inflammation and increase stem cell numbers providing an environment favorable for tissue regeneration.