Autologous transplantation of bone marrow mononuclear cells improved heart function after myocardial infarction
Abstract
AIM:
To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function.
METHODS:
Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining.
RESULTS:
BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation.
CONCLUSION:
Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.
Keywords:
To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function.
METHODS:
Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining.
RESULTS:
BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation.
CONCLUSION:
Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.