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.
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.
Authors: Jochen Müller-Ehmsen; Benjamin Krausgrill; Volker Burst; Kerstin Schenk; Uta C Neisen; Jochen W U Fries; Bernd K Fleischmann; Jürgen Hescheler; Robert H G Schwinger Journal: J Mol Cell Cardiol Date: 2006-09-14 Impact factor: 5.000
Authors: Birgit Assmus; Jörg Honold; Volker Schächinger; Martina B Britten; Ulrich Fischer-Rasokat; Ralf Lehmann; Claudius Teupe; Katrin Pistorius; Hans Martin; Nasreddin D Abolmaali; Torsten Tonn; Stefanie Dimmeler; Andreas M Zeiher Journal: N Engl J Med Date: 2006-09-21 Impact factor: 91.245
Authors: Wayne Rosamond; Katherine Flegal; Gary Friday; Karen Furie; Alan Go; Kurt Greenlund; Nancy Haase; Michael Ho; Virginia Howard; Brett Kissela; Bret Kissela; Steven Kittner; Donald Lloyd-Jones; Mary McDermott; James Meigs; Claudia Moy; Graham Nichol; Christopher J O'Donnell; Veronique Roger; John Rumsfeld; Paul Sorlie; Julia Steinberger; Thomas Thom; Sylvia Wasserthiel-Smoller; Yuling Hong Journal: Circulation Date: 2006-12-28 Impact factor: 29.690
Authors: Feng Cao; Koen E A van der Bogt; Amir Sadrzadeh; Xiaoyan Xie; Ahmad Y Sheikh; Haichang Wang; Andrew J Connolly; Robert C Robbins; Joseph C Wu Journal: Stem Cells Dev Date: 2007-12 Impact factor: 3.272
Authors: John Terrovitis; Matthias Stuber; Amr Youssef; Steve Preece; Michelle Leppo; Eddy Kizana; Michael Schär; Gary Gerstenblith; Robert G Weiss; Eduardo Marbán; M Roselle Abraham Journal: Circulation Date: 2008-03-10 Impact factor: 29.690
Authors: Anna V Naumova; Niranjan Balu; Vasily L Yarnykh; Hans Reinecke; Charles E Murry; Chun Yuan Journal: J Cardiovasc Pharmacol Ther Date: 2014-03-30 Impact factor: 2.457
Authors: Cajetan Lang; Sebastian Lehner; Andrei Todica; Guido Boening; Mathias Zacherl; Wolfgang-Michael Franz; Bernd Joachim Krause; Peter Bartenstein; Marcus Hacker; Robert David Journal: Eur J Nucl Med Mol Imaging Date: 2014-07-26 Impact factor: 9.236
Authors: Johannes A Govaert; Rutger-Jan Swijnenburg; Sonja Schrepfer; Xiaoyan Xie; Koen E A van der Bogt; Grant Hoyt; William Stein; Katherine J Ransohoff; Robert C Robbins; Joseph C Wu Journal: J Heart Lung Transplant Date: 2009-09-26 Impact factor: 10.247