Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium.
We aimed to optimize non-viral transfection of human stromal cell derived factor (SDF-1alpha) gene into skeletal myoblasts (SkM) and, transplant these cells to establish transient SDF-1alpha gradient to favor extra-cardiac stem cell translocation into infarcted heart. Optimized conditions for transfection of SDF-1alpha gene into syngenic SkM were achieved using FuGene6/phSDF-1alpha (3:2v/w, 4 h transfection) with 125 microM ZnCl(2) (p<0.001). After characterization for transgene overexpression by immunostaining, ELISA and PCR, the cells were transplanted in female rat model of myocardial infarction. Thirty-six rats were grouped (n=12/group) to receive 70 microl DMEM without cells (group-1) or containing 1.5 x 10(6) non-transfected (group-2) or SDF-1alpha transfected SkM (group-3). On day 4 post-transplantation (in 4 animals/group), marked expression of SDF-1alpha/sry-gene (p=0.003), total Akt, phospho-Akt and Bcl2 was observed in group-3. The number of CD31(+), C-kit(+) and CD34(+) cells was highest in group-3 hearts (p<0.01). Blood vessel density in group-3 was higher in both scar and peri-scar regions (p<0.001) as compared with other groups. Echocardiography showed improved indices of left ventricle contractile function and remodeling in group-3 (p<0.05) as compared with groups-1 and -2. We conclude that ex vivo SDF-1alpha transgene delivery promotes stem and progenitor cell migration to the heart, activates cell survival signaling and enhances angiomyogenesis in the infarcted heart.
Elmadbouh
I
I
Department of Pathology and Laboratory Medicine, 231-Albert Sabin Way, University of Cincinnati, Cincinnati, OH 45267-0529, USA.
Haider
Husnain Kh
HKh
Jiang
Shujia
S
Idris
Niagara Muhammad
NM
Lu
Gang
G
Ashraf
Muhammad
M
D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC