Skeletal muscle fibres form by fusion of mesoderm progenitors called myoblasts. After birth, muscle fibres do not increase in number but continue to grow in size because of fusion of satellite cells, ...the postnatal myogenic cells, responsible for muscle growth and regeneration. Numerous studies suggest that, on transplantation, non-myogenic cells also may contribute to muscle regeneration. However, there is currently no evidence that such a contribution represents a natural developmental option of these non-myogenic cells, rather than a consequence of experimental manipulation resulting in cell fusion. Here we show that pericytes, transgenically labelled with an inducible Alkaline Phosphatase CreERT2, but not endothelial cells, fuse with developing myofibres and enter the satellite cell compartment during unperturbed postnatal development. This contribution increases significantly during acute injury or in chronically regenerating dystrophic muscle. These data show that pericytes, resident in small vessels of skeletal muscle, contribute to its growth and regeneration during postnatal life.
Different cardiac stem/progenitor cells have been recently identified in the post-natal heart. We describe here the identification, clonal expansion and characterization of self-renewing progenitors ...that differ from those previously described for high spontaneous cardiac differentiation. Unique coexpression of endothelial and pericyte markers identify these cells as cardiac mesoangioblasts and allow prospective isolation and clonal expansion from the juvenile mouse ventricle. Cardiac mesoangioblasts express many cardiac transcription factors and spontaneously differentiate into beating cardiomyocytes that assemble mature sarcomeres and express typical cardiac ion channels. Cells similarly isolated from the atrium do not spontaneously differentiate. When injected into the ventricle after coronary artery ligation, cardiac mesoangioblasts efficiently generate new myocardium in the peripheral area of the necrotic zone, as they do when grafted in the embryonic chick heart. These data identify cardiac mesoangioblasts as committed progenitors, downstream of earlier stem/progenitor cells and suitable for the cell therapy of a subset of juvenile cardiac diseases.
The POCUS Certification Academy, a subdivision of Inteleos, a non-profit certification organization, is striving to promote global standards and international certifications in the field of POCUS to ...enhance clinician proficiency and ensure patient safety. By offering relevant rigorous assessments, developing continuing education requirements, and promoting the use of point-of-care ultrasound worldwide, the POCUS Certification Academy is laying the foundation for the highest global standards in POCUS credentialing.
Dysferlin deficiency leads to a peculiar form of muscular dystrophy due to a defect in sarcolemma repair and currently lacks a therapy. We developed a cell therapy protocol with wild-type adult ...murine mesoangioblasts. These cells differentiate with high efficiency into skeletal muscle in vitro but differ from satellite cells because they do not express Pax7. After intramuscular or intra-arterial administration to SCID/BlAJ mice, a novel model of dysferlinopathy, wild-type mesoangioblasts efficiently colonized dystrophic muscles and partially restored dysferlin expression. Nevertheless, functional assays performed on isolated single fibers from transplanted muscles showed a normal repairing ability of the membrane after laser-induced lesions; this result, which reflects gene correction of an enzymatic rather than a structural deficit, suggests that this myopathy may be easier to treat with cell or gene therapy than other forms of muscular dystrophies.
Aims Our objective was to test whether progenitor cell proliferation and differentiation potential may vary depending upon the disease of the donor. Methods and results Human cardiac mesoangioblasts ...were isolated from cardiac muscle biopsies of patients undergoing open heart surgery for correction of mitral regurgitation following an acute myocardial infarction (MR-MI) or correction of mitral and aortic regurgitation with ensuing left ventricular hypertrophy (MAR-LVH). The cells express surface markers and cardiac genes similar to mouse cardiac mesoangioblasts; they have limited self-renewing and clonogenic activity and are committed mainly to cardiogenesis. Although cardiac differentiation can be induced by 5-azacytidine or by co-culture with rat neonatal cardiomyocytes, human cells do not contract spontaneously like their mouse counterparts. When locally injected in the infarcted myocardium of immunodeficient mice, cardiac mesoangioblasts generate a chimeric heart that contains human myocytes and some capillaries; likewise, they colonize chick embryo hearts when transplanted in ovo. At variance with cells from patients with MR-MI, when isolation was performed on biopsies from MAR-LVH, cells could be isolated in much lower numbers, proliferated less extensively and failed to differentiate. Conclusion Cardiac mesoangioblasts are present in the human heart but this endogenous progenitor population is progressively exhausted, possibly by continuous and inefficient regeneration attempts.
The aim of this study was to investigate the growth and development of animals produced from demi-embryos and compare them with whole embryos from fetus to adult life. To achieve this, calves ...produced from fresh demi-embryos and whole embryos were individually transferred and monitored from 60 days of pregnancy until slaughter at 550 days. Ultrasound scans were conducted on fetuses at 60 and 90 days to evaluate the biparietal, abdominal, umbilical cord, orbital, and aorta diameters. Subsequently, morphological traits of newborn calves were measured at 0, 7, and 21 days (N = 18). Live weight was recorded at birth, weaning, and every 30 days thereafter until slaughter at 550 days. The growth curve of each group was modeled using logistic regression, and the factors of the respective functions were compared. As early as 60 days of pregnancy, ultrasound evaluations revealed no morphometric differences between fetuses produced from demi-embryos and those from whole embryos. This lack of differentiation persisted in the morphometric evaluations of newborns up to 21 days of age, as well as in live weight and the growth curve from birth to slaughter. Moreover, there were no significant differences between the groups in terms of rib eye area and fat thickness evolution. Consequently, individuals from demi-embryos exhibited no discernible disparities to those whole embryos in growth and development from 60 days of gestation, through birth, and into adulthood.
•Development and growth of bovine calves demi-embryos.•Bisected embryos lose around 50% of their cell mass.•At day 60, no differences are detected between fetuses from demi and whole embryos.•Newborn calves from demi and whole embryos are not significantly different.•Cattle produced from demi-embryos grow and develop similarly to those from whole ones.
Background. Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we ...determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF).
Methods. An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h).
Results.
In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation.
Conclusions. In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.
OBJECTIVE: To test whether very early resumption of ambulation after femoral cardiac catheterisation is feasible and safe in patients with stable symptoms. DESIGN: Prospective study in a selected ...group of men and women undergoing elective cardiac catheterisation, with next day physical inspection. SETTING: Inpatient study. SUBJECTS: Two hundred consecutive ambulant patients submitted to diagnostic cardiac catheterisation through the femoral arterial route using 5F catheters: a femoral right heart study was done at the same time in 40 patients (20%). RESULTS: No patient had major complications during the study. Early ambulation was not allowed in two patients (1%) because of haematoma formation immediately after sheath removal, and in seven (3%) because of poor haemostasis or haematoma on inspection at 3 h. Early ambulation was interrupted in two patients (1%) because of transient arterial hypotension on standing in one, and the patient's preference in the other. Of 189 patients who resumed full ambulation at 3 h, one (0.5%) had a groin haematoma on discharge the next morning. Overall, haematoma 12 h after cardiac catheterisation was present in seven of the 200 patients initially included in the study (3.5%). None of the 191 patients with attempted early mobilisation had signs or symptoms of vascular complications one month or later after discharge. CONCLUSION: Supervised resumption of ambulation 3 h after uncomplicated cardiac studies with 5F femoral arterial catheters is safe and feasible in most ambulant patients undergoing elective cardiac catheterisation.
Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic ...progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined.
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