Abstract 1073: Monitoring Peri-Implant Neovascularization Driven by Bone Marrow Progenitor Cells Using an in situ Oxygen Sensor
The progress in the field of implantable cardiovascular devices is blocked by the poorly vascularized fibrous capsule developing around them. We tested the hypothesis that co-implantation of autologous endothelial progenitor cells (EPC) stimulates neovascularization around the implants, and that a novel implantable device containing an oxygen-sensitive EPR spin probe would allow in vivo monitoring of the peri-implant microcirculation.
Methods: The device consisted of a bio-compatible cylinder (10 mm in length and 4 mm in diameter), limited at one end by an aluminum oxide nanoporous filter with pores of 200 nm. Inside and in contact with the filter, we placed a layer of oxygen-sensitive EPR-detectable microcrystals of LiNc-BuO, developed by our group. The device was calibrated by exposure of the animals to breathed carbogen to measure absolute pO2 values, noninvasively, from the site of placement, for extended periods of time. 21 devices were implanted subcutaneously in C57/Bl6 mice:
surrounded by 500 μl of Matrigel (control groups) or
with Matrigel containing autologous 106 cells/implant of bone marrow-derived c-kit+/sca-1+ cells, isolated by MACS.
Oxygenation of the implants was measured daily in the first week, and weekly for the next month. At the end of the experiments, the tissues surrounding the implants were collected for immunohistochemistry.
Results: While initially there was no difference in the oxygen levels across experimental groups, at day 7 the EPC-treated devices indicated 166±23% (p<0.05) higher oxygenation as compared to the other two conditions. This difference remained significantly higher for up to 1 month, with a decrease to 62.5±18% (p<0.05). At this time, immunohistochemistry revealed abundant collagen deposition and F4/80 positive macrophages and giant cells around the control implants, but a virtually total replacement of the fibrous capsule by a highly vascularized (CD31 positive) adipose layer, in the cell treatment group.
Conclusion: We successfully developed a progenitor cells-based strategy to maintain the vascularization at implantation site, by eliminating the fibrous capsule formation, and a novel implantable oxygen-sensing probe to monitor angiogenesis for cardiovascular applications.