No abstract

BackgroundThis study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective.Methods and resultsYoung male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p < 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p < 0.001). The ST-segment resolution (>80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p < 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p < 0.001).ConclusionEarly intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI.

Background/purpose Previously we demonstrated up-regulation of matrix metalloproteinase-3 ( MMP-3 ) in human osteoblasts under compression and in bony specimens of experimental orthodontic tooth movement (OTM). Here, we studied the temporal characteristics of compression stimulation in human and mouse osteoblast cell lines, and generated a transgenic mouse model for assessing the MMP-3 expression during OTM. Materials and methods We investigated MMP-3 expressions in human and murine osteoblasts through RT-PCR and luciferase assay, after compressive force loading. Inhibitors were added to identify the possible mechanisms for signal transduction. A human MMP-3 promoter was isolated, cloned and transfected to generate a transgenic mouse with a green fluorescent protein reporter. OTM was then initiated to observe the location and time course of transcriptional regulation of MMP-3 signals. Results We found changes in the transcription of MMP-3 in response to mechanical force applied to both human and mouse osteoblast cell lines, suggesting that the response is positive across species. Cloned human MMP-3 promoter may cause the response of luciferase to 1% compression. Moreover, p38 inhibitor exerted a down-regulatory effect on MMP-3 promoter expression, although the inhibitory effect didn't reach a significant level. In the transgenic mouse OTM model, we again found increased expression of MMP-3 in response to mechanical force loading around the periodontal ligament. Conclusion Mechanical force can stimulate MMP-3 expression, possibly through the p38 MAPK pathway, with its strongest signal occurring at 24 h. The mechanical responsiveness in MMP-3 promoter regions can be observed in both humans and rodents in vitro and in vivo.