title: Percutaneous adventitial delivery of allogeneic bone marrow-derived stem cells via infarct-related artery improves long-term ventricular function in acute myocardial infarction.
abstract: Acute myocardial infarction (AMI) results in ischemic damage and death of cardiomyocytes and loss of vasculature. Stem cell therapy has emerged as a potentially promising strategy for maximizing cardiac function following ischemic injury. Issues of cell source, delivery, and quantification  of response have challenged development of clinically viable strategies. In this study we investigate the effects of a well-defined bone marrow-derived allogeneic cell product delivered by catheter directly to the myocardium via the infarct-related vessel on global and regional measures of  left ventricular (LV) function in a porcine model of anterior wall myocardial infarction. Multipotent adult progenitor cells (MAPCs) were derived and expanded from the bone marrow of a donor Yorkshire pig. Anterior wall myocardial infarction (AMI) was induced by 90 min of mid-LAD occlusion  using a balloon catheter. Two days after AMI was induced, either vehicle (Plasma Lyte-A, n = 7), low-dose (20 million, n = 6), or high-dose (200 million, n = 6) MAPCs were delivered directly to the myocardium via the infarct-related vessel using a transarterial microsyringe  catheter-based delivery system. Echocardiography was used to measure LV function as a function of time after AMI. Animals that received low-dose cell treatment showed significant improvement in regional and global LV function and remodeling compared to the high-dose or control animals. Direct  myocardial delivery of allogeneic MAPCs 2 days following AMI through the vessel wall of the infarct-related vessel is safe and results in delivery of cells throughout the infarct zone and improved cardiac function despite lack of long-term cell survival. These data further support the hypothesis  of cell-based myocardial tissue repair by a paracrine mechanism and suggest a clinically translatable strategy for delivering cells at any time after AMI to modulate cardiac remodeling and function.
authors: Regenerative Medicine Department, Athersys, Inc., Cleveland, OH 44309, USA.
authors: Satish
authors: S
authors: Medicetty
authors: Dominik
authors: D
authors: Wiktor
authors: Nicholas
authors: N
authors: Lehman
authors: Amy
authors: A
authors: Raber
authors: Zoran B
authors: ZB
authors: Popovic
authors: Robert
authors: R
authors: Deans
authors: Anthony E
authors: AE
authors: Ting
authors: Marc S
authors: MS
authors: Penn
mesh_terms: D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002404:Catheterization; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A