Final Report Summary - HEARTREGENERATION (Transplantation of magnetic-labelled vascular cells and cardiomyocytes ... in a bioactive injectable gel for myocardium regeneration after infarct)
Cardiovascular diseases remain the number one cause of death in the western world. Human embryonic stem cells (hESCs) represent a promising source of cells for the treatment of cardiovascular diseases because of their unlimited cell propagation and ability to give rise to different cell types, including cardiomyocytes, endothelial and smooth muscle cells.
Cardiomyocytes isolated from hESCs have been shown to form new myocardium after infarct; however, the functional recovery of the myocardium was low and the functional coupling was inexistent since the cardiomyocytes were observed within the scar and not in direct contact with host cardiomyocytes (Laflamme et al., Nat Biotechnol, 2007). We anticipate that the transplantation of these cells using an injectable bioactive gel will enhance cell retention and viability at the injection site.
This projects aims to evaluate the neovascularisation and myocardium functional recovery after transplanting hESC-derived cardiomyocytes and vascular cells in a gel into a myocardial infarction animal model. In addition, this project aims to develop a protocol to monitor non-invasively in vivo cell grafting.
In the first two years of the project, we have developed a synthetic matrix metalloproteinase-responsive hydrogel to encapsulate vascular cells. We have shown that the incorporation of thymosin beta-4 in the matrix facilitated endothelial cell attachment, survival and vascular-like network formation. In a separate work, we have shown that smooth muscle cells derived from hESCs could be encapsulated in a fibrin gel and the three-dimensional environment contributed for cell maturation. Finally, we have demonstrated that the transplant of hESC-derived endothelial and smooth muscle cells in the heart after infarction preserved contractile performance. In the last two years of the project, we have studied the pro-survival and pro-angiogenic effect of vascular endothelial growth factor tethered to a three-dimensional (3D) matrix. In addition, we have developed a nanoparticle formulation to label cells and track them non-invasively by magnetic resonance imaging (MRI).
Cardiomyocytes isolated from hESCs have been shown to form new myocardium after infarct; however, the functional recovery of the myocardium was low and the functional coupling was inexistent since the cardiomyocytes were observed within the scar and not in direct contact with host cardiomyocytes (Laflamme et al., Nat Biotechnol, 2007). We anticipate that the transplantation of these cells using an injectable bioactive gel will enhance cell retention and viability at the injection site.
This projects aims to evaluate the neovascularisation and myocardium functional recovery after transplanting hESC-derived cardiomyocytes and vascular cells in a gel into a myocardial infarction animal model. In addition, this project aims to develop a protocol to monitor non-invasively in vivo cell grafting.
In the first two years of the project, we have developed a synthetic matrix metalloproteinase-responsive hydrogel to encapsulate vascular cells. We have shown that the incorporation of thymosin beta-4 in the matrix facilitated endothelial cell attachment, survival and vascular-like network formation. In a separate work, we have shown that smooth muscle cells derived from hESCs could be encapsulated in a fibrin gel and the three-dimensional environment contributed for cell maturation. Finally, we have demonstrated that the transplant of hESC-derived endothelial and smooth muscle cells in the heart after infarction preserved contractile performance. In the last two years of the project, we have studied the pro-survival and pro-angiogenic effect of vascular endothelial growth factor tethered to a three-dimensional (3D) matrix. In addition, we have developed a nanoparticle formulation to label cells and track them non-invasively by magnetic resonance imaging (MRI).