Circulation (New York, N.Y.), 2004-03, Vol.109 (12), p.1543-1549
2004
Details
- Autor(en) / Beteiligte
- Titel
- Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms
- Ist Teil von
- Circulation (New York, N.Y.), 2004-03, Vol.109 (12), p.1543-1549
- Ort / Verlag
- Hagerstown, MD: Lippincott Williams & Wilkins
- Erscheinungsjahr
- 2004
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Bone marrow cell therapy is reported to contribute to collateral formation through cell incorporation into new or remodeling vessels. However, the possible role of a paracrine contribution to this effect is less well characterized. Murine marrow-derived stromal cells (MSCs) were purified by magnetic bead separation of cultured bone marrow. The release of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and monocyte chemoattractant protein-1 (MCP-1) was demonstrated by analysis of MSC conditioned media (MSC-CM). MSC-CM enhanced proliferation of endothelial cells and smooth muscle cells in a dose-dependent manner; anti-VEGF and anti-FGF antibodies only partly attenuated these effects. Balb/C mice (n=10) underwent distal femoral artery ligation, followed by adductor muscle injection of 1x10(6) MSCs 24 hours later. Compared with controls injected with media (n=10) or mature endothelial cells (n=8), distal limb perfusion improved, and mid-thigh conductance vessels increased in number and total cross-sectional area. MSC injection improved limb function and appearance, reduced the incidence of auto-amputation, and attenuated muscle atrophy and fibrosis. After injection, labeled MSCs were seen dispersed between muscle fibers but were not seen incorporated into mature collaterals. Injection of MSCs increased adductor muscle levels of bFGF and VEGF protein compared with controls. Finally, colocalization of VEGF and transplanted MSCs within adductor tissue was demonstrated. MSCs secrete a wide array of arteriogenic cytokines. MSCs can contribute to collateral remodeling through paracrine mechanisms.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0009-7322eISSN: 1524-4539DOI: 10.1161/01.cir.0000124062.31102.57Titel-ID: cdi_proquest_miscellaneous_71778046
- Format
- –
- Schlagworte
- Animals, Biological and medical sciences, Blood and lymphatic vessels, Cardiology. Vascular system, Cells, Cultured - secretion, Cells, Cultured - transplantation, Chemokine CCL2 - secretion, Collateral Circulation, Culture Media, Conditioned - pharmacology, Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous, Endothelial Cells - cytology, Endothelial Cells - drug effects, Endothelial Cells - metabolism, Endothelium, Vascular - cytology, Endothelium, Vascular - drug effects, Fibroblast Growth Factor 2 - secretion, Fibrosis, Growth Substances - secretion, Hindlimb - blood supply, Hypoxia-Inducible Factor 1, alpha Subunit, Immunomagnetic Separation, Injections, Intramuscular, Ischemia - physiopathology, Ischemia - therapy, Medical sciences, Mesenchymal Stem Cell Transplantation, Mice, Mice, Inbred BALB C, Muscle, Skeletal - blood supply, Muscle, Skeletal - pathology, Muscle, Smooth, Vascular - cytology, Muscle, Smooth, Vascular - drug effects, Muscular Atrophy - etiology, Muscular Atrophy - pathology, Myocytes, Smooth Muscle - cytology, Myocytes, Smooth Muscle - drug effects, Myocytes, Smooth Muscle - metabolism, Paracrine Communication, Placenta Growth Factor, Pregnancy Proteins - secretion, Stromal Cells - transplantation, Transcription Factors - biosynthesis, Transcription Factors - genetics, Vascular Endothelial Growth Factor A - secretion