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.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Medicetty S,Wiktor D,Lehman N,Raber A,Popovic ZB,Deans R,Ting AE,Penn MS

doi

10.3727/096368911X603657

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

1109-20

issue

6

eissn

0963-6897

issn

1555-3892

pii

ct0192medicetty

journal_volume

21

pub_type

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