Stem Cells and Acellular Preparations in Bone Regeneration/Fracture Healing: Current Therapies and Future Directions.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.

Catecholamine response to exercise in patients with non-obstructive hypertrophic cardiomyopathy.

KEY POINTS: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). As a result, the majority of patients with HCM deliberately reduce their habitual physical activity after diagnosis and this lifestyle change puts them at risk for sequelae of a sedentary lifestyle: weight gain, hypertension, hyperlipidaemia, insulin resistance, coronary artery disease, and increased morbidity and mortality. We show that plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold, a parameter that can be defined during cardiopulmonary exercise testing, but rise rapidly at higher intensities of exercise. These findings suggest that cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM. ABSTRACT: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). However, the impact of exercise intensity on plasma catecholamine levels among HCM patients has not been rigorously defined. We conducted a prospective observational case-control study of men with non-obstructive HCM and age-matched controls. Laboratory-based cardiopulmonary exercise testing coupled with serial phlebotomy was used to define the relationship between exercise intensity and plasma catecholamine levels. Compared to controls (C, n = 5), HCM participants (H, n = 9) demonstrated higher left ventricular mass index (115 ± 20 vs. 90 ± 16 g/m2 , P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P < 0.001) but similar body mass index, resting heart rate, peak oxygen consumption (H = 40 ± 13 vs. C = 42 ± 7 ml/kg/min, P = 0.81) and heart rate at the ventilatory threshold (H = 78 ± 6 vs. C = 78 ± 4% peak heart rate, P = 0.92). During incremental effort exercise in both groups, concentrations of adrenaline and noradrenaline were unchanged through low- and moderate-exercise intensity until reaching a catecholamine threshold (H = 82 ± 4 vs. C = 85 ± 3% peak heart rate, P = 0.86) after which levels of both molecules rose rapidly. In patients with mild non-obstructive HCM, plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold but rise rapidly at higher intensities of exercise. Routine cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM.