PMID- 23146336 OWN - NLM STAT- MEDLINE DCOM- 20140829 LR - 20181202 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 22 IP - 12 DP - 2013 TI - Angiogenesis following cell injection is induced by an excess inflammatory response coordinated by bone marrow cells. PG - 2381-92 LID - 10.3727/096368912X658863 [doi] AB - 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)-1alpha, MIP-1beta, 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. FAU - Hattori, Hidemi AU - Hattori H AD - Division of Biomedical Engineering, Research Institute, National Defense Medical College, Saitama, Japan. FAU - Amano, Yoshiko AU - Amano Y FAU - Habu-Ogawa, Yoshiko AU - Habu-Ogawa Y FAU - Ando, Takahiro AU - Ando T FAU - Takase, Bonpei AU - Takase B FAU - Ishihara, Masayuki AU - Ishihara M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121108 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (CXCR4 protein, mouse) RN - 0 (Receptors, CXCR4) RN - 0 (Vascular Endothelial Growth Factor A) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Adipose Tissue/cytology MH - Animals MH - Bone Marrow Cells/*cytology/*immunology/metabolism MH - *Bone Marrow Transplantation MH - Cell Movement/drug effects MH - Ear/blood supply MH - Hepatocyte Growth Factor/metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - *Neovascularization, Physiologic/drug effects MH - Receptors, CXCR4/immunology/metabolism MH - Tail/blood supply MH - Vascular Endothelial Growth Factor A/metabolism EDAT- 2012/11/14 06:00 MHDA- 2014/08/30 06:00 CRDT- 2012/11/14 06:00 PHST- 2012/11/14 06:00 [entrez] PHST- 2012/11/14 06:00 [pubmed] PHST- 2014/08/30 06:00 [medline] AID - ct0768hattori [pii] AID - 10.3727/096368912X658863 [doi] PST - ppublish SO - Cell Transplant. 2013;22(12):2381-92. doi: 10.3727/096368912X658863. Epub 2012 Nov 8.