Abstract 2875: Effect of Timing of Bone Marrow Cell Delivery on Cell Viability and Cardiac Recovery Following Myocardial Infarction
Background: Despite ongoing clinical trails, the optimal time for delivery of bone marrow mononuclear cells (BMC) following myocardial infarction (MI) is unclear. We compared the viability and effect on cardiac function of BMC transplanted in the acute and sub-acute inflammatory phase of MI.
Methods and results: The time-course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) following LAD ligation. Mac-1+Gr-1high neutrophil infiltration peaked at day 4. BMC were harvested from transgenic FVB mice expressing firefly luciferase and GFP. 2.5x106 BMC were injected into the left ventricle of wild-type FVB mice either immediately (group I) or 7 days (group II) after MI, or after a sham procedure (n=8/group). In vivo bioluminescent imaging (BLI) showed early signal increase in group I at day 7, followed by a trend towards improved BMC survival in group II that persisted until BLI signal reached background levels after 42 days (Fig 1⇓). Compared to controls (MI + saline injection), echocardiography showed significant preservation of fractional shortening at 4 weeks (II vs saline; P<0.01) and 6 weeks (I+II vs saline; P<0.05), but no significant difference between groups I and II. FACS analysis of BMC injected hearts at day 7 revealed that GFP+ BMCs expressed hematopoietic (CD45, Mac-1, Gr-1) markers, but not progenitor (sca-1, c-kit), endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers.
Conclusion: Timing of BMC delivery has a minimal effect on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMC tend to adopt inflammatory cell phenotypes.