title: Stimulation of peri-implant vascularization with bone marrow-derived progenitor cells: monitoring by in vivo EPR oximetry.
abstract: The poorly vascularized fibrous capsule that develops around implantable biomedical devices (for drug delivery, biosensors, etc.) severely limits their applications. We tested the hypotheses that co-implantation of bone marrow-derived progenitor cells could stimulate the vascularization of implants. To assess the presence of functional peri-implant microvasculature, we developed a novel model of implanted device containing an oxygen (O(2))-sensing spin probe (detectable using electron paramagnetic resonance) placed inside a nanoporous filter-limited capsule. These devices were implanted subcutaneously in C57/Bl6 mice alone, with the addition of a Matrigel plug in front of the filter, or with the addition of Matrigel containing equal proportions of c-kit(+) and stem cell antigen-1(+) bone marrow-derived cells. Implants partial pressure of O(2) (pO(2)) were recorded non-invasively and periodically for up to 10 weeks. Tissue surrounding the implants was collected for immunohistochemistry. Initially, there were no differences in pO(2) between the experimental groups. After 3 weeks, the devices supplied with progenitor cells showed more than twice the O(2) concentrations as controls. This difference remained significant for 4 more weeks and then started to decrease slightly, still being 6 mmHg higher than in the controls at 10 weeks post-implantation. Collagen deposition was detected around the control implants, along with F4/80-positive macrophages and giant cells. In the plugs collected from the cell treatment group, we found an active process of adipogenesis, accompanied by neovascularization, and a highly vascularized adipose layer surrounding the implants. In conclusion, we successfully developed a cell therapy-type strategy to maintain vascularization around implanted devices using co-administration of bone marrow-derived progenitor cells, and we demonstrated a novel O(2)-sensing method to functionally monitor neovascularization in vivo.
authors.affiliation: Davis Heart and Lung Research Institute, Department of Internal Medicine/Cardiology, Ohio State University, Columbus, Ohio, USA.
authors.forename: Omar I
authors.initials: OI
authors.lastname: Butt
authors.forename: Robert
authors.initials: R
authors.lastname: Carruth
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kutala
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Nicanor I
authors.initials: NI
authors.lastname: Moldovan
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D018380:Hematopoietic Stem Cell Transplantation; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010092:Oximetry; D010313:Partial Pressure; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit