PMID- 25202910 OWN - NLM STAT- MEDLINE DCOM- 20150528 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 9 DP - 2014 TI - GM-CSF treated F4/80+ BMCs improve murine hind limb ischemia similar to M-CSF differentiated macrophages. PG - e106987 LID - 10.1371/journal.pone.0106987 [doi] LID - e106987 AB - Novel cell therapy is required to treat critical limb ischemia (CLI) as many current approaches require repeated aspiration of bone marrow cells (BMCs). The use of cultured BMCs can reduce the total number of injections required and were shown to induce therapeutic angiogenesis in a murine model of hind limb ischemia. Blood flow recovery was significantly improved in mice treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent BMCs that secreted inflammatory cytokines. Angiogenesis, lymphangiogenesis, and blood flow recovery ratio were significantly higher in the GM-CSF-cultured F4/80+ macrophage (GM-Mo)-treated group compared with controls. Furthermore, Foxp3+ cell numbers and tissue IL-10 concentrations were significantly increased compared with controls. There was no significant difference in blood flow recovery between GM-Mo and M-CSF-cultured F4/80+ macrophages (M-Mo). Thus, GM-Mo were associated with improved blood flow in hind limb ischemia similar to M-Mo. The selective methods of culturing and treating GM-Mo cells similar to M-Mo cells could be used clinically to help resolve the large number of cells required for BMC treatment of CLI. This study demonstrates a novel cell therapy for CLI that can be used in conjunction with conventional therapy including percutaneous intervention and surgical bypass. FAU - Kuwahara, Go AU - Kuwahara G AD - Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. FAU - Nishinakamura, Hitomi AU - Nishinakamura H AD - Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. FAU - Kojima, Daibo AU - Kojima D AD - Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. FAU - Tashiro, Tadashi AU - Tashiro T AD - Department of Cardiovascular Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. FAU - Kodama, Shohta AU - Kodama S AD - Department of Regenerative Medicine and Transplantation, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140909 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 130068-27-8 (Interleukin-10) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Bone Marrow Cells/metabolism/*physiology MH - Cell- and Tissue-Based Therapy/methods MH - Disease Models, Animal MH - Extremities/*physiology MH - Forkhead Transcription Factors/metabolism MH - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology MH - Interleukin-10/metabolism MH - Ischemia/metabolism/*therapy MH - Lymphangiogenesis/physiology MH - Macrophage Colony-Stimulating Factor/metabolism/*physiology MH - Macrophages/metabolism/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL PMC - PMC4159294 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/09/10 06:00 MHDA- 2015/05/29 06:00 PMCR- 2014/09/09 CRDT- 2014/09/10 06:00 PHST- 2014/02/20 00:00 [received] PHST- 2014/08/11 00:00 [accepted] PHST- 2014/09/10 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2015/05/29 06:00 [medline] PHST- 2014/09/09 00:00 [pmc-release] AID - PONE-D-14-05423 [pii] AID - 10.1371/journal.pone.0106987 [doi] PST - epublish SO - PLoS One. 2014 Sep 9;9(9):e106987. doi: 10.1371/journal.pone.0106987. eCollection 2014.