Jarvie Journal - College of Dental Medicine - Columbia University

Volume 56, Spring 2013
Circulating Endothelial Progenitor Cells in Periodontitis
T. Spinell, D. Jönsson, A. Vrettos, R.T. Demmer, R. Celenti, S. Chen, M. Kebschull, P.N. Papapanou
Division of Periodontics, Section of Oral and Diagnostic Sciences,
Columbia University College of Dental Medicine, NY, NY
Introduction: Circulating Endothelial Progenitor Cells (cEPCs) are bone marrow-derived stem cells that are
recruited into the blood stream and can home to sites of endothelial injury where they can develop into functional
endothelial cells. cEPCs have attracted attention as markers for endothelial function and due to their potential use
in therapeutic angiogenesis, but also because of their association with a number of pathologic conditions,
including sepsis, atherosclerosis, rheumatoid arthritis and inflammatory bowel disease. From a biological
plausibility point of view, there are two distinct alternatives through which periodontal infections may be related
to cEPC levels: The transient bacteremias and the state of systemic inflammation and endothelial damage that are
associated with periodontitis may induce enhanced EPC recruitment from the bone marrow, resulting in an
increase in the levels of cEPCs in the bloodstream. On the other hand, vascular endothelial damage may result in
cEPC homing to sites of endothelial injury, and systemic inflammation may impair cEPC proliferation and
increase cEPC apoptosis resulting in an exhaustion of the cEPC pool and lower cEPC levels.
Objective: The aim of this cross-sectional study was to compare the levels of endothelial progenitor cells in the
peripheral blood of patients with moderate to severe periodontitis to that of age-, gender- and menstruation cyclematched
periodontally healthy controls.
Materials and Methods: A total of 110 participants, men and women between 25-65 years of age with >20 teeth
present, have been enrolled to date. These included periodontitis patients (> 2 teeth per quadrant with a probing
depth of ≥ 5 mm and clinical attachment loss of ≥3 mm as well as bleeding on probing at ≥30% of their sites) and
periodontally healthy controls (no teeth with probing depth of >5 mm or interproximal attachment loss > 2mm).
Individuals using antibiotics within 3 months of recruitment, those diagnosed with systemic conditions known to
affect periodontitis or EPC levels (i.e., hypertension, hypercholesterolemia, rheumatoid arthritis), pregnant
women and current smokers were excluded.
All participants underwent a comprehensive evaluation of their periodontal status including assessments of
plaque, bleeding on probing, probing depth (PD) and clinical attachment loss (CAL). Body mass index (BMI) and
systolic blood pressure (SBP) were recorded, and a 60 ml blood sample was obtained. Hemangioblastic cEPC
levels were assessed as a percentage of viable peripheral blood mononuclear cells using flow cytometry, based on
the expression of progenitor cell markers CD34 and CD133 and of endothelial cell marker KDR (kinase insert
domain receptor). Monocytic cEPC levels were assessed after culture of peripheral blood mononuclear cells and
subsequent characterization using fluorescent microscopy on the basis of LDL uptake and lectin staining.
Results and Conclusions: Thus far, hemangioblastic cEPC levels have been assessed in 88 subjects (46
periodontitis patients and 42 periodontally healthy controls) and monocytic cEPC levels in 45 subjects (22
periodontitis patients and 23 controls). Analyses based on 42 matched pairs showed higher hemangioblastic cEPC
levels in periodontitis patients than controls (p=0.057) but comparable monocytic cEPC levels (p=0.443).
Regression analyses adjusting for age, gender, BMI and SBP showed that the % of pockets with probing depth ≥ 4
mm (p=0.046) or ≥ 6 mm (p=0.008) and the % of sites with attachment loss ≥ 6 mm (p=0.019) were associated
with hemangioblastic cEPC levels. Levels of hemangioblastic and monocytic cEPCs were positively correlated
(r=0.392, p=0.008).
Discussion: Poor periodontal status appears to be positively associated with cEPC levels, indicating an increased
mobilization of EPCs from the bone marrow in response to endothelial injury in periodontitis. The kinetics of this
mobilization and its association with vascular repair and function need to be elucidated further.
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