Abstract 456: Vascular Delivery of Autologous Mononuclear Cells After Brief Culture is Associated with Worsening of Vessel Repair and Endothelial Function
Background. Local delivery of peripheral blood mononuclear cells (PBMC) cultured toward an endothelial phenotype for 7–21 days is associated with significant improvement in endothelial function and vessel repair after arterial injury. In this study we have evaluated the effect of minimal culture modification of PBMCs in an effort to bring this treatment closer to clinical applicability.
Methods and results. A rabbit model of carotid artery injury was used. PBMCs were harvested from 30 ml of peripheral blood and cultured for 24h in endothelial growth media, with (n=6) or without (n=6) addition of fetal bovine serum. On day 2, animals underwent balloon carotid injury followed by local delivery of PBMCs to one lumen (average 2.2x105 per artery, range 1.5–3.0x105) and vehicle (200 μl phosphate buffered saline) to the contralateral artery, with a 20min dwell time before restoration of flow. A significantly higher intima/media ratio was observed in PBMC-treated arteries harvested after 28 days (1.05±0.95 vs 0.62±0.61, p<0.05). Carotid rings showed a trend towards worsening of endothelial-dependent vasoreactivity in PBMC treated arteries (% max relaxation to acetylcholine 26±10 vs 45±13 with saline, p=0.07). Addition of serum to culture media had no significant effect on the outcome. Conditioned media of PBMCs from healthy individuals showed presence of MCP-1 at 24 hours but not at 7 days, as well as higher levels of IL-8 at 24h on cytokine array studies.
Conclusion. Local delivery of PBMCs following one day in culture is associated with worsening of vessel repair after arterial injury. These results are in sharp contrast with our previous findings of a beneficial effect of 7 and 21 day culture PBMCs in the same animal model, and suggest that culture modification of PBMC for longer duration is a necessary step. The effects may be related to downregulation of MCP-1 and IL-8 in culture conditions.