Human marrow-isolated adult multilineage-inducible (MIAMI) cells protect against peripheral vascular ischemia in a mouse model |
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| Authors: | Amirali Rahnemai-Azar Gianluca D'Ippolito Lourdes A. Gomez Teresita Reiner Roberto I. Vazquez-Padron Carlos Perez-Stable Bernard A. Roos Si M. Pham Paul C. Schiller |
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| Affiliation: | 1. Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea;2. Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Republic of Korea;3. Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea;4. Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam, Republic of Korea;5. Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea;6. Department of Internal Medicine, Soonchunhyang University, Seoul, Republic of Korea;7. Hyonam Kidney Laboratory, Soonchunhyang University, Seoul, Republic of Korea;8. Department of Surgery, School of Medicine, Soonchunhyang University, Cheonan 330-930, Republic of Korea;9. Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, Republic of Korea;10. BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, Republic of Korea;1. Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;2. Institute for Bionanotechnology in Medicine, Department of Medicine, Northwestern University, Chicago, IL, USA;3. Department of Materials Science and Engineering, Department of Chemistry, Northwestern University, Evanston, IL, USA;4. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;5. Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA |
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| Abstract: | Background aimsThe treatment of peripheral vascular disease (PVD) with stem cells potentially offers a promising strategy. We tested marrow-isolated adult multilineage-inducible (MIAMI) cells to induce neovascularization in a mouse model of critical hindlimb ischemia (CLI).MethodsCLI was induced in the right hindlimb of Balb/C mice. One million MIAMI cells, normally grown at 3% O2, were injected in the adductor muscle along the ischemic region. All animals (n = 11 per group) were immunosuppressed with cyclosporine daily for the entire period. Human foreskin fibroblast (HFF) cells and phosphate-buffered saline (PBS) were used as controls. Blood perfusion in the ischemic right and non-ischemic left hindlimbs was measured.ResultsCompared with animals receiving HFF cells or PBS, MIAMI cells significantly improved blood perfusion, necrosis and inflammation in the ischemic limb. A fraction of injected MIAMI cells expressed CD31 and von Willebrand factor (vWF). MIAMI cells in vitro, under pro-angiogenic growth conditions, differentiated into endothelial-like cells and expressed endothelial markers such as CD31 and vWF, determined by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), and CD31 and kinase insert domain receptor (KDR), determined by immunofluorescence. Moreover, MIAMI cells formed vascular endothelial-like tubules in the presence of matrigel. Bioplex immunoassay analysis showed increased secretion of angiogenic/anti-inflammatory factors by the MIAMI cells under 3% O2 compared with 21% O2, including monocyte chemoattractant protein-1 (MCP-1), fractalkine (Ftk), growth-related oncogene (GRO), vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8. Furthermore, transcripts for anti-inflammatory molecules stanniocalcin-1 (STC-1) and tumor necrosis factor-α-stimulated gene 6 (TSG-6) were up-regulated several fold.ConclusionsMIAMI cells can be very useful for patients affected by CLI. MIAMI cells promote blood vessel formation and reduce inflammation and necrosis in ischemic tissue. |
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