Comparison of different adult stem cell types for treatment of myocardial ischemia
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Comparison of different adult stem cell types for treatment of myocardial ischemia. / van der Bogt, Koen E A; Sheikh, Ahmad Y; Schrepfer, Sonja; Hoyt, Grant; Cao, Feng; Ransohoff, Katherine J; Swijnenburg, Rutger-Jan; Pearl, Jeremy; Lee, Andrew; Fischbein, Michael; Contag, Christopher H; Robbins, Robert C; Wu, Joseph C.
In: CIRCULATION, Vol. 118, No. 14 Suppl, 30.09.2008, p. 121-129.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Comparison of different adult stem cell types for treatment of myocardial ischemia
AU - van der Bogt, Koen E A
AU - Sheikh, Ahmad Y
AU - Schrepfer, Sonja
AU - Hoyt, Grant
AU - Cao, Feng
AU - Ransohoff, Katherine J
AU - Swijnenburg, Rutger-Jan
AU - Pearl, Jeremy
AU - Lee, Andrew
AU - Fischbein, Michael
AU - Contag, Christopher H
AU - Robbins, Robert C
AU - Wu, Joseph C
PY - 2008/9/30
Y1 - 2008/9/30
N2 - BACKGROUND: A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction.METHODS AND RESULTS: Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially received one cell type (5x10(5)) or PBS. Cell survival was measured by BLI and by TaqMan PCR. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements. Fluc expression correlated with cell number in all groups (r(2)>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes.CONCLUSIONS: This is the first study to show that compared to MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function.
AB - BACKGROUND: A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction.METHODS AND RESULTS: Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb), and fibroblasts (Fibro) expressing firefly luciferase (Fluc) and green fluorescence protein (GFP) were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=70) underwent LAD ligation and intramyocardially received one cell type (5x10(5)) or PBS. Cell survival was measured by BLI and by TaqMan PCR. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements. Fluc expression correlated with cell number in all groups (r(2)>0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes.CONCLUSIONS: This is the first study to show that compared to MSC, SkMB, and Fibro, MN exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function.
KW - Animals
KW - Bone Marrow Cells
KW - Bone Marrow Transplantation
KW - Cell Survival
KW - Echocardiography
KW - Female
KW - Fibroblasts/transplantation
KW - Green Fluorescent Proteins/genetics
KW - Luciferases, Firefly/genetics
KW - Male
KW - Mesenchymal Stem Cell Transplantation
KW - Mice
KW - Mice, Inbred Strains
KW - Mice, Transgenic
KW - Myoblasts, Skeletal/transplantation
KW - Myocardial Infarction/diagnostic imaging
KW - Myocardial Ischemia/diagnostic imaging
KW - Reproducibility of Results
KW - Stem Cell Transplantation
KW - Ventricular Function, Left
U2 - 10.1161/CIRCULATIONAHA.107.759480
DO - 10.1161/CIRCULATIONAHA.107.759480
M3 - SCORING: Journal article
C2 - 18824743
VL - 118
SP - 121
EP - 129
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 14 Suppl
ER -