Background-Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium. Methods and Results-A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, -myosin heavy chain, ␣-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs. Conclusions-The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.
Objectives
To characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT).
Background
Plaque erosion and calcified nodule have not been systematically investigated in vivo.
Methods
One hundred and twenty-six patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or others using a new set of diagnostic criteria for OCT.
Results
The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest compared with those with PR and OCT-CN (53.8±13.1 years vs. 60.6±11.5 years, 65.1±5.0 years, p=0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS (NSTE-ACS) was more common in patients with OCT-erosion (61.5% vs. 29.1%, p=0.008) and OCT-CN (100% vs. 29.1%, p<0.001). OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p<0.001), thicker fibrous cap (169.3±99.1 μm vs. 60.4±16.6 μm, p<0.001), and smaller lipid arc (202.8±73.6° vs. 275.8±60.4°, p<0.001) than PR. The diameter stenosis was least severe in OCT-erosion followed by OCT-CN and PR (55.4±14.7% vs. 66.1±13.5% vs. 68.8±12.9%, p<0.001).
Conclusions
OCT is a promising modality for identifying OCT-erosion and OCT-CN in vivo. OCT-erosion is a frequent finding in patients with ACS, especially in those with NSTE-ACS and younger patients. OCT-CN is the least common etiology for ACS and is more common in older patients.
Vascular delivery of mesenchymal stem cells (MSCs) following myocardial infarction is under clinical investigation. Little is known about the microvascular fate of MSCs. We used intravital microscopy of rat cremaster muscle microcirculation to track intraarterially delivered MSCs. Rat MSCs (average diameter, 23 µm) were bolused into the ipsilateral common iliac artery. Interrogation of an arteriole–venule pair revealed that 92 ± 7% (n = 6) of MSCs arrest and interrupt flow during first pass at the precapillary level, resulting in decreased flow in the feeding arteriole (velocity decreased from 6.3 ± 1.0 to 4.6 ± 1.3 mm/sec; P<0.001). MSC deformability evaluated using filtration through polycarbonate membranes revealed that the cortical tension of MSCs (0.49 ± 0.07 dyne/cm, n = 9) was not different from that of circulating mononuclear cells (0.50 ± 0.05 dyne/cm, n = 7). When intravital microscopy was performed 3 days following injection, the number of MSCs in the cremaster further decreased to 14% of the initial number, because of cell death in situ. In vivo labeling of the basement membrane revealed that at 1 day, the surviving cells were spread out on the luminal side of the microvessel, whereas at 3 days, they integrated in the microvascular wall. Despite their deformability, intraarterially delivered MSCs entrap at the precapillary level because of their large size, with a small proportion of surviving MSCs integrating in a perivascular niche.
Background:
Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 6-15% of MI and disproportionately affects women. Scientific statements recommend multi-modality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) to assess mechanisms of MINOCA.
Methods:
In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of MI. If invasive coronary angiography revealed <50% stenosis in all major arteries, multi-vessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and non-ischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible.
Results:
Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intra-plaque cavity or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% of participants undergoing CMR (62/116). A non-ischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome or non-ischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% of the women with multi-modality imaging (98/116), higher than with OCT alone (p<0.001) or CMR alone (p=0.001). An ischemic etiology was identified in 63.8% of women with MINOCA (74/116), a non-ischemic etiology was identified in 20.7% (24/116), and no mechanism was identified in 15.5% (18/116).
Conclusions:
Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI. Identification of the etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention.
Clinical Trial Registration:
URL: https://clinicaltrials.gov Unique Identifier: NCT02905357
CTO PCI is currently being performed with high success and acceptable complication rates among various experienced centers in the United States, Europe, and Russia. (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention [PROGRESS CTO]; NCT02061436).
The absolute number of TCFA is 3 times greater in nonsevere stenosis than in severe stenosis. It is, however, twice as likely for a lesion to be TCFA in cases of severe stenosis than in nonsevere stenosis. Moreover, TCFA in severely-stenotic areas had more features of plaque vulnerability.
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