PMID- 23219511 OWN - NLM STAT- MEDLINE DCOM- 20130522 LR - 20171116 IS - 1097-6809 (Electronic) IS - 0741-5214 (Linking) VI - 57 IP - 4 DP - 2013 Apr TI - Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia. PG - 1090-9 LID - S0741-5214(12)01943-X [pii] LID - 10.1016/j.jvs.2012.08.121 [doi] AB - OBJECTIVE: The use of bone marrow cells (BMCs) in therapeutic angiogenesis has been studied extensively. However, the critical paracrine effects of this treatment are still unclear. Therefore, we studied autotransfusable cells that produce vascular endothelial growth factor (VEGF), especially VEGF-C. METHODS: Male C57BL/6 mice with hind limb ischemia were administered intramuscular injections of phosphate-buffered saline as controls, or unsorted BMCs, sorted CD11b(+), or CD11b(-) cells from BMCs, and recombinant VEGF-C. To evaluate the treatments, perfusion was measured by laser Doppler scanning performed on days 0, 1, 3, 7, 14, 21, and 28. A functional assay was performed in parallel, with mice traversing an enclosed walkway. Capillary density was determined by directly counting vessels stained positive with von Willebrand factor at individual time points. Lymphangiogenesis was assessed by LYVE-1 positive cells. RESULTS: Postischemic recovery of hind limb perfusion significantly improved in BMC, CD11b(+), and VEGF-C treatment groups compared with the control groups, as assessed by laser Doppler scanning. On early operative days 1 and 3, the blood flow recovery ratio was higher in the CD11b(+)-treated group compared with BMC and VEGF-C treatment groups. In the functional assay, the VEGF-C group dramatically recovered compared with the control group. The capillary/myofiber ratio in the thigh muscle and number of LYVE-1 positive cells was higher in the CD11b(+) and VEGF-C groups than in controls. Furthermore, expression of VEGF-A, VEGF-C, and VEGF receptor messenger ribonucleic acid and protein was observed in CD11b(+) cells. CONCLUSIONS: The VEGF-C derived from CD11b(+) cells play a critical role in angiogenesis and lymphangiogenesis in a murine model of hind limb ischemia. Consequently, treatment with self-CD11b(+) cells accelerated recovery from ischemia and may be a promising therapeutic strategy for peripheral arterial disease patients. CI - Copyright (c) 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. FAU - Kuwahara, Go AU - Kuwahara G AD - Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. FAU - Nishinakamura, Hitomi AU - Nishinakamura H FAU - Kojima, Daibo AU - Kojima D FAU - Tashiro, Tadashi AU - Tashiro T FAU - Kodama, Shohta AU - Kodama S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121207 PL - United States TA - J Vasc Surg JT - Journal of vascular surgery JID - 8407742 RN - 0 (Antibodies, Neutralizing) RN - 0 (CD11b Antigen) RN - 0 (Recombinant Proteins) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factor C) RN - 0 (vascular endothelial growth factor A, mouse) RN - 0 (vascular endothelial growth factor C, mouse) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Animals MH - Antibodies, Neutralizing/pharmacology MH - Bone Marrow Cells/immunology/*metabolism MH - *Bone Marrow Transplantation MH - CD11b Antigen/*metabolism MH - Capillaries/metabolism/physiopathology MH - Disease Models, Animal MH - Hindlimb MH - Injections, Intramuscular MH - Ischemia/genetics/metabolism/physiopathology/*therapy MH - Laser-Doppler Flowmetry MH - Lymphangiogenesis MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Skeletal/*blood supply MH - *Neovascularization, Physiologic/drug effects MH - Recombinant Proteins/administration & dosage MH - Recovery of Function MH - Regional Blood Flow MH - Time Factors MH - Vascular Endothelial Growth Factor A/metabolism MH - Vascular Endothelial Growth Factor C/administration & dosage/genetics/*metabolism MH - Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/metabolism EDAT- 2012/12/12 06:00 MHDA- 2013/05/23 06:00 CRDT- 2012/12/11 06:00 PHST- 2012/06/14 00:00 [received] PHST- 2012/08/27 00:00 [revised] PHST- 2012/08/29 00:00 [accepted] PHST- 2012/12/11 06:00 [entrez] PHST- 2012/12/12 06:00 [pubmed] PHST- 2013/05/23 06:00 [medline] AID - S0741-5214(12)01943-X [pii] AID - 10.1016/j.jvs.2012.08.121 [doi] PST - ppublish SO - J Vasc Surg. 2013 Apr;57(4):1090-9. doi: 10.1016/j.jvs.2012.08.121. Epub 2012 Dec 7.