Dataset Information

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

ABSTRACT: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n?=?7), the single bolus group (SB) (n?=?7, 15 × 10(7) ASCs), or the divided dose group (DD) (n?=?7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured.The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4?±?0.9%, 3.7?±?0.7%, and -0.4?±?0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3?±?1.8 and -11.5?±?2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9?±?0.2, 0.8?±?0.1, and 0.2?±?0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687?±?317/µL, 3,454?±?787/µL, and 1,928?±?457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area.Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

SUBMITTER: Jun Hong S

PROVIDER: S-EPMC5896329 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

Jun Hong Soon S Rogers Pamela I PI Kihlken John J Warfel Jessica J Bull Chris C Deuter-Reinhard Maja M Feng Dongni D Xie Jie J Kyle Aaron A Merfeld-Clauss Stephanie S Johnstone Brian H BH Traktuev Dmitry O DO Chen Peng-Sheng PS Lindner Jonathan R JR March Keith L KL

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 20150424 2

<h4>Objectives</h4>The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.<h4>Methods</h4>Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive da ...[more]

PMID: 24905889

Similar Datasets

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”.

Project description:ObjectivesCardiovascular magnetic resonance-feature tracking (CMR-FT) enables quantification of myocardial deformation and may be used as an objective measure of myocardial involvement in ST-elevation myocardial infarction (STEMI). We sought to investigate the associations between myocardial dyssynchrony parameters and myocardium damage for STEMI.MethodsWe analyzed 65 patients (45-80 years old) with anterior STEMI after primary percutaneous coronary intervention during 3-7 days [observational (STEMI) group] and 60 healthy volunteers [normal control (NC) group]. Myocardial dyssynchrony parameters were derived, including global and regional strain, radial rebound stretch and displacement, systolic septal time delay, and circumferential stretch.ResultsCMR characteristics, including morphologic parameters such as left ventricular ejection fraction (LVEF) (45.3% ± 8.2%) and myocardium damage in late gadolinium enhancement (LGE) (19.4% ± 4.7% LV), were assessed in the observation group. The global radial strain (GRS) and global longitudinal strain (GLS) substantially decreased in anterior STEMI compared with the NC group (GRS: 19.4% ± 5.1% vs. 24.8% ± 4.0%, P < 0.05; GLS: -10.1% ± 1.7% vs. -13.7% ± 1.0%, P < 0.05). Among 362 infarcted segments, radial and circumferential peak strains of the infarcted zone were the lowest (14.4% ± 3.2% and -10.7% ± 1.6%, respectively). The radial peak displacement of the infarct zone significantly decreased (2.6 ± 0.4 mm) (P < 0.001) and manifested in the circumferential displacement (3.5° ± 0.7°) in the STEMI group (P < 0.01). As microvascular occlusion (MVO) was additionally present, some strain parameters were significantly impaired in LGE+/MVO+ segments (radial strain [RS]: 12.2% ± 2.1%, circumferential strain [CS]: -9.6% ± 0.7%, longitudinal strain [LS]: -6.8% ± 1.0%) compared to LGE+/MVO- (RS: 14.6% ± 3.2%, CS: -10.8% ± 1.8%, LS: -9.2% ± 1.3%) (P < 0.05). When the extent of transmural myocardial infarction is greater than 75%, the parameter of the systolic septal delay (mean, 148 ms) was significantly reduced compared to fewer degrees of infarction (P < 0.01).ConclusionIn anterior STEMI, the infarcted septum swings in a bimodal mode, and myocardial injury reduces the radial strain contractility. A more than 75% transmural degree was the septal strain-contraction reserve cut-off point.

Dataset Information

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

Publications

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets