Abstract 20861: Depletion of BM Progenitor Cell Reserve, Rather Than Progenitor Cell Mobilization is Associated With Major Events in Severe Limb Ischemia
Introduction: Lower numbers of progenitor cells (PCs) in peripheral blood (PB) have been associated with cardiovascular events in high-risk populations. It is currently unknown what causes the reduction in PB-PC numbers: whether it is depletion of the bone marrow (BM) PC reserve, or a reduced mobilization of PCs from BM. In this study we examine the relative contribution of PB- and BM-PC numbers to the prediction of Amputation-Free Survival (AFS) in patients with Severe Limb-Ischemia (SLI).
Methods and Results: PB and BM were obtained from 160 patients enrolled in a trial investigating BM cell-therapy for SLI. Samples were incubated with antibodies against CD34, KDR, CD133, CD184, CD14, CD105, CD140b, and CD31; cell populations were enumerated by flow cytometry and CFU-GM and BFU-E were obtained. Median follow-up was 3 years. Higher PB CD34+ and CD133+ PC numbers were related to AFS (Both Hazard Ratio [HRevent]=0.56, p=0.003 and p=0.0007 respectively). There was no association of AFS with the other cell populations in PB. BM-PC numbers correlated with PB-PC numbers and showed similar HRs for AFS. A further subdivision based on relative BM- and PB PC numbers showed that BM CD34+ and CD133+ PC numbers, rather than mobilization, were associated with AFS (figure 1a-d).
Conclusion: Both PB and BM PC numbers are independently associated with AFS and show very similar risk profiles. Our data suggest that depletion of the BM PC reserve, rather than decreased PC mobilization underlies the association between PB PC numbers and cardiovascular risk.
Author Disclosures: H. Gremmels: None. M. Teraa: None. F.C. van Rhijn-Brouwer: None. D.A. Papazova: None. J.O. Fledderus: None. M.C. Verhaar: None.
- © 2016 by American Heart Association, Inc.