Dataset Information

Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

ABSTRACT: Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We?hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p?=?0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p?=?0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p?=?0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.

SUBMITTER: Li X

PROVIDER: S-EPMC3689724 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

Li Xiaorong X Zhang Fengxiang F Song Guixian G Gu Weijuan W Chen Minglong M Yang Bing B Li Dianfu D Wang Daowu D Cao Kejiang K

PloS one 20130621 6

Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS ...[more]

PMID: 23805264

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Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses We report temporal and regional changes in steady state mRNA levels in the mouse LV following a surgically-induced AMI. Three regions of the infarcted LV were surveyed: IF, FW and IVS. For each region, mRNA levels were assayed at t=0 and six time points after occlusion of the left anterior descending coronary artery (t = 15 min, 1 h, 4 h, 12 h, 24 h, 48 h). As control, an identical time course was carried out in the mouse LV after sham surgery in which the suture was passed under the artery, but not ligated. For sham surgical mice and naïve mice (t=0), the IVS and the LV free wall were harvested and assayed. The AMI and sham time courses were repeated for a total of two independent repetitions of the experiment. For each repetition, 96 GeneChips were hybridized. Thus, for two repetitions, 192 GeneChips (2 x 96) were hybridized. In addition, the naïve time point was assayed a second time during Repetition 1 for six additional GeneChips (two tissues x three chips). The overall total number of samples is 198 GeneChips (192 + 6). Total RNA was isolated from each individual tissue sample. Equal weights of total RNA from 4-10 mice were combined for each LV region, time point and treatment. Copy RNA mixtures were synthesized from each total RNA pool and hybridized to the Affymetrix GeneChip set MG U74 v2 (A, B, and C) that carries 36,899 probe sets. The global normalization of fluorescence emissions for the 198 GeneChips used in this study and their conversion to relative transcript concentrations measured in relative fluorescence units (RFU) was conducted using Robust Multi-array Averaging (RMA; www.bioconductor.org). Each of the 198 Accessions is titled as follows: time point / treatment / tissue, repetition, GeneChip. The additional assays of naïve mice in Repetition 1 are labeled “Naive2”.

Dataset Information

Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

Publications

Intramyocardial Injection of Pig Pluripotent Stem Cells Improves Left Ventricular Function and Perfusion: A Study in a Porcine Model of Acute Myocardial Infarction.

Similar Datasets

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