Abstract 3499: Combined Stromal Cell-Derived Factor-1 and Ligand Enhanced Matrix Mobilizes Bone Marrow Progenitor Cells for Neovascularization and Perfusion of Ischemic Tissue
Background: In this study, microspheres containing stromal cell-derived factor-1 (SDF-1) were added to a collagen matrix containing sialyl LewisX (sLeX). A bone marrow (BM) transplant and hindlimb ischemia model was used to evaluate the ability of this “combined matrix” to improve progenitor cell mobilization and recruitment, and vascularization of ischemic tissue.
Methods: The marrow of C57BL/6J mice (n=36) was reconstituted with green fluorescent protein (GFP)+ BM cells from C57BL/6-Tg(ACTbEGFP)10sb/J donors. After 6 weeks, hindlimb ischemia was induced and limbs were injected with:
collagen matrix, or
Over 2 weeks, blood mononuclear cells were analyzed by flow cytometry, and laser Doppler perfusion analysis was performed.
Results: Marker expression (post/pre ligation ratio) on circulating GFP+ mononuclear cells are presented in the Table⇓. At early time points, more CXCR4+, flk+ and c-kit+ cells were mobilized after treatment with combined matrix compared to all other treatments. At later time points (7–14 days), more CXCR4+, flk+ and c-kit+ circulating cells were observed after combined matrix and sLeX-collagen treatment, compared to PBS and collagen. Arteriole density was greatest for combined matrix (10.0±1.0/mm2) and sLeX-collagen treatment (9.6±0.5/mm2) compared to PBS (2.0±0.3/mm2) and collagen (6.5±0.4; p≤0.002). Perfusion (ischemic/non-ischemic ratio) was increased in combined matrix (1.41±0.09) and sLeX-collagen (1.23±0.06) treated hindlimbs, versus PBS (0.69±0.06) and collagen (0.96±0.04; p≤0.006).
Conclusions: Treatment with SDF-1 microspheres and sLeX-collagen matrices increases early and late mobilization of BM cells after treatment, and results in greater vascular density and improved perfusion. This study demonstrates a strategy by which enhanced matrices may modify the endogenous BM progenitor cell response and improve cell-based angiogenic therapy.