PMID- 20839998 OWN - NLM STAT- MEDLINE DCOM- 20110726 LR - 20180629 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 13 IP - 2 DP - 2011 Feb TI - Human marrow-isolated adult multilineage-inducible (MIAMI) cells protect against peripheral vascular ischemia in a mouse model. PG - 179-92 LID - 10.3109/14653249.2010.515579 [doi] AB - BACKGROUND AIMS: The 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). METHODS: CLI was induced in the right hindlimb of Balb/C mice. One million MIAMI cells, normally grown at 3% O(2), 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. RESULTS: Compared 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% O(2) compared with 21% O(2), 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-alpha-stimulated gene 6 (TSG-6) were up-regulated several fold. CONCLUSIONS: MIAMI cells can be very useful for patients affected by CLI. MIAMI cells promote blood vessel formation and reduce inflammation and necrosis in ischemic tissue. FAU - Rahnemai-Azar, Amirali AU - Rahnemai-Azar A AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - D'Ippolito, Gianluca AU - D'Ippolito G FAU - Gomez, Lourdes A AU - Gomez LA FAU - Reiner, Teresita AU - Reiner T FAU - Vazquez-Padron, Roberto I AU - Vazquez-Padron RI FAU - Perez-Stable, Carlos AU - Perez-Stable C FAU - Roos, Bernard A AU - Roos BA FAU - Pham, Si M AU - Pham SM FAU - Schiller, Paul C AU - Schiller PC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100915 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Angiogenic Proteins) RN - 0 (Cytokines) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (von Willebrand Factor) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Adult Stem Cells/*physiology/*transplantation MH - Angiogenic Proteins/metabolism MH - Animals MH - Bone Marrow Cells MH - Cell Differentiation MH - Cytokines/metabolism MH - Fluorescent Antibody Technique MH - Hindlimb/*blood supply/injuries MH - Humans MH - Inflammation/therapy MH - Ischemia/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Necrosis MH - *Neovascularization, Physiologic MH - Peripheral Vascular Diseases/*therapy MH - Platelet Endothelial Cell Adhesion Molecule-1/genetics/metabolism MH - Regional Blood Flow MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stem Cell Transplantation MH - Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism MH - von Willebrand Factor/genetics/metabolism EDAT- 2010/09/16 06:00 MHDA- 2011/07/27 06:00 CRDT- 2010/09/16 06:00 PHST- 2010/09/16 06:00 [entrez] PHST- 2010/09/16 06:00 [pubmed] PHST- 2011/07/27 06:00 [medline] AID - S1465-3249(11)70494-7 [pii] AID - 10.3109/14653249.2010.515579 [doi] PST - ppublish SO - Cytotherapy. 2011 Feb;13(2):179-92. doi: 10.3109/14653249.2010.515579. Epub 2010 Sep 15.