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Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy
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Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy
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Journal Article
Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy
2003
Overview
Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy.
We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography.
Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control
vs SDF-1-expressing cardiac fibroblasts mean 7·2 [SD 3·4]
vs 33·2 [6·0] cells/mm
2, n=4 per group, p<0·02) resulting in greater left-ventricular mass (1·24 [0·29]
vs 1·57 [0·27] g) and better cardiac function (shortening fraction 9·2 [4·9]
vs 17·2 [4·2]%, n=8 per group, p<0·05).
These findings show that SDF-1 is sufficient to induce therapeutic stem-cell homing to injured myocardium and suggest a strategy for directed stem-cell engraftment into injured tissues. Our findings also indicate that therapeutic strategies focused on stem-cell mobilisation for regeneration of myocardial tissue must be initiated within days of myocardial infarction unless signalling for stem-cell homing is reestablished.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Cell Division - drug effects
/ Cell Movement - drug effects
/ Chemokines, CXC - physiology
/ Colony-Stimulating Factors - administration & dosage
/ Colony-Stimulating Factors - pharmacology
/ Granulocyte Colony-Stimulating Factor - administration & dosage
/ Granulocyte Colony-Stimulating Factor - pharmacology
/ Heart
/ Myocardial Ischemia - surgery
/ Pluripotent Stem Cells - drug effects
/ Pluripotent Stem Cells - physiology
/ Rats
/ Stem Cell Transplantation - methods
/ Tissues
