PMID- 15023891
OWN - NLM
STAT- MEDLINE
DCOM- 20040715
LR  - 20220409
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 109
IP  - 12
DP  - 2004 Mar 30
TI  - Local delivery of marrow-derived stromal cells augments collateral perfusion 
      through paracrine mechanisms.
PG  - 1543-9
AB  - BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: MSCs secrete a wide array of arteriogenic cytokines. 
      MSCs can contribute to collateral remodeling through paracrine mechanisms.
FAU - Kinnaird, T
AU  - Kinnaird T
AD  - Cardiovascular Research Institute, Washington, DC 20010, USA. 
      tim.kinnaird@medstar.net
FAU - Stabile, E
AU  - Stabile E
FAU - Burnett, M S
AU  - Burnett MS
FAU - Shou, M
AU  - Shou M
FAU - Lee, C W
AU  - Lee CW
FAU - Barr, S
AU  - Barr S
FAU - Fuchs, S
AU  - Fuchs S
FAU - Epstein, S E
AU  - Epstein SE
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
DEP - 20040315
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Growth Substances)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Pgf protein, mouse)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 144589-93-5 (Placenta Growth Factor)
SB  - IM
EIN - Circulation. 2005 Jul 26;112(4):e73
MH  - Animals
MH  - Cells, Cultured/metabolism/transplantation
MH  - Chemokine CCL2/metabolism
MH  - *Collateral Circulation
MH  - Culture Media, Conditioned/pharmacology
MH  - Endothelial Cells/cytology/drug effects/metabolism
MH  - Endothelium, Vascular/cytology/drug effects
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Fibrosis
MH  - Growth Substances/*metabolism
MH  - Hindlimb/*blood supply
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunomagnetic Separation
MH  - Injections, Intramuscular
MH  - Ischemia/physiopathology/*therapy
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Skeletal/blood supply/pathology
MH  - Muscle, Smooth, Vascular/cytology/drug effects
MH  - Muscular Atrophy/etiology/pathology
MH  - Myocytes, Smooth Muscle/cytology/drug effects/metabolism
MH  - *Paracrine Communication
MH  - Placenta Growth Factor
MH  - Pregnancy Proteins/metabolism
MH  - Stromal Cells/*transplantation
MH  - Transcription Factors/biosynthesis/genetics
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2004/03/17 05:00
MHDA- 2004/07/16 05:00
CRDT- 2004/03/17 05:00
PHST- 2004/03/17 05:00 [pubmed]
PHST- 2004/07/16 05:00 [medline]
PHST- 2004/03/17 05:00 [entrez]
AID - 01.CIR.0000124062.31102.57 [pii]
AID - 10.1161/01.CIR.0000124062.31102.57 [doi]
PST - ppublish
SO  - Circulation. 2004 Mar 30;109(12):1543-9. doi: 10.1161/01.CIR.0000124062.31102.57. 
      Epub 2004 Mar 15.