ABSTRACT
Skeletal muscle stem cells (MuSCs) have been proposed as suitable candidates for cell therapy in muscular disorders since they exhibit good capacity for myogenic regeneration. However, for better therapeutic outcomes, it is necessary to isolate human MuSCs from a suitable tissue source with high myogenic differentiation. In this context, we isolated CD56+CD82+ cells from the extra eyelid tissue of young and aged patients, and tested in vitro myogenic differentiation potential. In the current study, myogenic cells derived from extra eyelid tissue were characterized and compared with immortalized human myogenic cells. We found that myogenic cells derived from extra eyelid tissue proliferated and differentiated myofibers in vitro, and restored DYSTROPHIN or PAX7 expression after transplantation with these cells in mice with Duchenne muscular dystrophy. Thus, human myogenic cells derived from extra eyelid tissue including the orbicularis oculi might be good candidates for stem cell-based therapies for treating muscular diseases.
Subject(s)
Cell Differentiation , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/metabolism , Stem Cell Transplantation , Stem Cells/cytology , Stem Cells/metabolism , Animals , Biomarkers , Cells, Cultured , Humans , Immunophenotyping , Mice , Muscular Dystrophy, Duchenne/therapy , PhenotypeABSTRACT
BACKGROUND AND PURPOSE: Although it has been reported that matrix metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in patients with hypertrophic cardiomyopathy (HCM), the impact of plasma MMP levels in patients with HCM is somewhat vague. METHODS AND SUBJECTS: Plasma levels of MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM patients with preserved LV ejection fraction (defined as LV ejection fraction more than 50%) caused by an identical frameshift mutation (S593fs: a one-base deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding protein C gene. RESULTS: MMP-2 levels were inversely related to LV ejection fraction (r(2)=-37, p=0.01). MMP-9 levels were inversely related to LV end-diastolic dimension (r(2)=-0.24, p=0.06) and positively related to the maximum LV wall thickness (r(2)=0.25, p=0.04). During follow-up period of 4.1 ± 1.2 years, LV ejection fraction decreased from 68.5 ± 7.4% to 64.9 ± 9% (p=0.03). Among clinical, echocardiographic findings at baseline and levels of biomarkers, high MMP-9 levels were only related to the decrease of LV ejection fraction from baseline to follow-up (r(2)=0.39, p=0.009). CONCLUSIONS: MMP-2 levels are related to reduced LV systolic function in HCM patients with preserved LV ejection fraction caused by an identical cardiac myosin-binding protein C gene abnormality. On the other hand, MMP-9 levels are associated with small LV size and the degree of LV hypertrophy and related to the deterioration in LV systolic function during follow-up. These results suggest that MMPs are important in the process of LV remodeling in HCM.
Subject(s)
Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Carrier Proteins/genetics , Frameshift Mutation , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 9/blood , Ventricular Remodeling , Adult , Biomarkers/blood , Cardiomyopathy, Hypertrophic/pathology , Cardiomyopathy, Hypertrophic/physiopathology , Echocardiography , Female , Follow-Up Studies , Heart Ventricles/pathology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Stroke Volume , Systole , Ventricular Function, LeftABSTRACT
BACKGROUND: In addition to sudden death, heart failure and stroke due to atrial fibrillation are important in patients with hypertrophic cardiomyopathy (HCM). The aim of the present study was to determine whether Doppler tissue imaging findings and plasma B-type natriuretic peptide (BNP) levels, which are widely used for risk stratification in several cardiovascular diseases, are useful for risk stratification in patients with HCM in a regional cohort. METHODS: One hundred thirty patients (82 men; mean age, 60 ± 16 years) with HCM were enrolled in this study. RESULTS: Twenty end points were observed during a mean follow-up period of 3.7 ± 1.7 years. Septal E/e' ratios and BNP levels in patients with events were higher than those in patients without events (17.4 ± 6.3 vs 10.6 ± 4.3, P < .0001, and 441 ± 304 vs 202 ± 174 pg/mL, P < .0001, respectively). By multivariate logistic regression analysis, a high septal E/e' ratio, in addition to a history of syncope and documentation of atrial fibrillation, was a significant predictor of combined end points. In contrast, plasma BNP levels were not a significant predictor of combined end points. CONCLUSION: Assessment by Doppler tissue imaging is useful for further risk stratification of patients with HCM.
