title: Angiogenesis following cell injection is induced by an excess inflammatory response coordinated by bone marrow cells.
abstract: The aim of this study was to identify novel angiogenic mechanisms underlying the regenerative process. To that end, interactions between adipose tissue-derived stromal cells (ASCs) and bone marrow cells (BMCs) were initially investigated using real-time fluorescence optical imaging. To monitor cell behavior in mice, we injected green fluorescent protein-positive (GFP(+)) BMCs into the tail vein and injected PKH26-labeled ASCs behind the ears. Angiogenesis and inflammation were observed at these sites via an optical imaging probe. Injected GFP(+) BMCs migrated from the blood vessels into the tissues surrounding the ASC injection sites. Many of the migrating GFP(+) BMCs discovered at the ASC injection sites were inflammatory cells, including Gr-1(+), CD11b(+), and F4/80(+) cells. ASCs cocultured with inflammatory cells secreted increased levels of chemokines such as macrophage inflammatory protein (MIP)-1α, MIP-1β, keratinocyte-derived chemokines, and monocyte chemotactic protein 1. Similarly, these ASCs secreted increased levels of angiogenic growth factors such as hepatocyte growth factor and vascular endothelial growth factor. However, when anti-CXC chemokine receptor type 4 antibody was injected at regular intervals, the migration of GFP(+) BMCs (especially Gr-1(+) and CD11b(+) cells) to ASC injection sites was inhibited, as was angiogenesis. The collective influence of the injected ASCs and BMC-derived inflammatory cells promoted acute inflammation and angiogenesis. Together, the results suggest that the outcome of cell-based angiogenic therapy is influenced not only by the injected cells but also by the effect of intrinsic inflammatory cells.
authors.affiliation: Division of Biomedical Engineering, Research Institute, National Defense Medical College, Saitama, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Amano
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Habu-Ogawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ando
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects; D004423:Ear / Q000098:blood supply; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D013623:Tail / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor