TY - JOUR
T1 - Enhancing efficacy of stem cell transplantation to the heart with a PEGylated fibrin biomatrix
AU - Zhang, Ge
AU - Hu, Qingsong
AU - Braunlin, Elizabeth A
AU - Suggs, Laura J.
AU - Zhang, Jianyi J
PY - 2008/6/1
Y1 - 2008/6/1
N2 - Bone marrow-derived mononuclear cell (BMNC) transplantation provides the possibility of rescue or regeneration of myocardium lost during acute myocardial infarction (AMI). The extensive death of transplanted cells and the lack of sustained engraftment may limit its application. We investigated whether delivery of BMNCs by an injectable PEGylated fibrin biomatrix that covalently binds hepatocyte growth factor (HGF) would enhance the rate of cell engraftment and improve cardiac function. Balb/C female mice with AMI secondary to left anterior descending coronary ligation were randomly assigned to one of six groups: the Saline control group (n = 8) received a myocardial injection of saline (50 μL); the Cell group (n = 10) received a myocardial injection in the peri-infarct and infarct zones consisting of 500,000 murine BMNCs suspended in 50 μL saline; and the Biomatrix + HGF (n = 9) and Biomatrix + HGF + Cell (n = 9) group hearts received the HGF-loaded injectable biomatrix (identical volume) with or without entrapped BMNCs. Control groups consisting of the biomatrix alone (n = 9) and Biomatrix + Cells (n = 9) without HGF were also included for comparison. The left ventricular (LV) function was measured by echocardiography at days 14 and 28 post-MI. All animals were euthanized 4 weeks after AMI and transplantation for evaluation of angiogenesis, apoptosis, and fibrosis by immunohistochemistry. Cell prevalence rate at 4 weeks increased 15-fold in hearts receiving the Biomatrix + HGF + Cell delivery (p < 0.01), which was accompanied by the lowest levels of apoptosis and the highest LV function recovery among the treated groups.
AB - Bone marrow-derived mononuclear cell (BMNC) transplantation provides the possibility of rescue or regeneration of myocardium lost during acute myocardial infarction (AMI). The extensive death of transplanted cells and the lack of sustained engraftment may limit its application. We investigated whether delivery of BMNCs by an injectable PEGylated fibrin biomatrix that covalently binds hepatocyte growth factor (HGF) would enhance the rate of cell engraftment and improve cardiac function. Balb/C female mice with AMI secondary to left anterior descending coronary ligation were randomly assigned to one of six groups: the Saline control group (n = 8) received a myocardial injection of saline (50 μL); the Cell group (n = 10) received a myocardial injection in the peri-infarct and infarct zones consisting of 500,000 murine BMNCs suspended in 50 μL saline; and the Biomatrix + HGF (n = 9) and Biomatrix + HGF + Cell (n = 9) group hearts received the HGF-loaded injectable biomatrix (identical volume) with or without entrapped BMNCs. Control groups consisting of the biomatrix alone (n = 9) and Biomatrix + Cells (n = 9) without HGF were also included for comparison. The left ventricular (LV) function was measured by echocardiography at days 14 and 28 post-MI. All animals were euthanized 4 weeks after AMI and transplantation for evaluation of angiogenesis, apoptosis, and fibrosis by immunohistochemistry. Cell prevalence rate at 4 weeks increased 15-fold in hearts receiving the Biomatrix + HGF + Cell delivery (p < 0.01), which was accompanied by the lowest levels of apoptosis and the highest LV function recovery among the treated groups.
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U2 - 10.1089/ten.tea.2007.0289
DO - 10.1089/ten.tea.2007.0289
M3 - Article
C2 - 18476809
AN - SCOPUS:45549084295
SN - 1937-3341
VL - 14
SP - 1025
EP - 1036
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
IS - 6
ER -