Abstract P1080: Periostin Is Induced During Cell-based Repair In The Sheep Model Of Myocardial Infarction

Abstract

Cardiac disease is the leading cause of death worldwide. Stem cell-based therapy may improve patient outcomes following a myocardial infarction. Our laboratory is studying the mechanistic basis by which neonatal Islet-1 positive cardiovascular progenitor cells (CPC) facilitate post infarct repair in the sheep model of myocardial infarction. Here, we addressed the hypothesis that periostin (POSTN) is induced in the cardiovascular repair zone following neonatal Islet-1+ cell-based repair. POSTN promotes cardiomyocyte proliferation, recruitment of M2 macrophages, epithelial-mesenchymal transition (EMT), migration, and angiogenesis. We examined human neonatal Islet-1+ cardiovascular progenitor cell clones isolated from several patients to initially determine whether or not POSTN was expressed in these cells. All clones expressed POSTN as shown by RT-PCR. The size of the amplified transcripts was confirmed by gel electrophoresis and POSTN expression in these clones was further confirmed by RNA sequencing. We then examined POSTN expression in the cardiovascular repair zone following myocardial infarction and cell transplantation in sheep. Sheep neonatal Islet-1+ CPC clones were used in this model of allogeneic cell-based repair. A myocardial infarction was induced in three Western sheep by left anterior descending coronary artery ligation. Ten million neonatal sheep Islet1+ cardiac progenitor cell clones isolated from 9 day old sheep were injected into the area surrounding the infarct site 3-4 weeks post infarction. RNA was isolated from the cardiovascular repair zone two months after cell injection. The non-infarcted region of the left ventricle and the left ventricle of normal, non-infarcted sheep were used as controls. POSTN transcripts were significantly elevated in the cell-treated cardiovascular repair zone of all three sheep, as identified by qRT-PCR relative to controls. Periostin levels were elevated between 6 and 255 fold in the repair zone relative to the non-infarcted region of the heart. Our data shows that POSTN is expressed in human Islet-1+ neonatal cardiovascular progenitor cells and that POSTN levels are induced during cell-based cardiovascular repair in the sheep model of myocardial infarction.