Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.     

A hybrid form of cardiac resynchronisation therapy in patients with failing systemic right ventricles

INTRODUCTION: Late systemic right ventricular (RV) dysfunction after atrial redirection surgery is common. Patients may require cardiac transplantation in early adulthood. METHODS: We undertook cardiac resynchronisation (CRT)/defibrillator therapy in two patients as a bridge to transplantation. RESULTS: Two males (aged 24, 110 kg and 26 years, 106 kg); having undergone a Mustard procedure for dextro-transposition of the great arteries at 7 and 6 months of age respectively, presented with impaired systemic RV function and New York Heart Association III symptoms. Both patients had dual chamber pacemakers in-situ for sinus bradycardia. Upgrade to CRT was performed by conserving the existing endocardial leads and placement of epicardial electrodes. One demonstrated sustained improvement over a 24 month follow-up period. CONCLUSION: A hybrid CRT strategy is feasible in patients with failing systemic RVs and pre-existent endocardial dual chamber pacemakers. Appropriate patient selection criteria and optimum lead placement, however, still needs further evaluation in this population.     

“The Chisel Test”—A useful operative, technique for determining adequate, compression during arthrodesis

Healing of an arthrodesis occurs optimally when the prepared joint surfaces are held rigidly under compression [1]. We routinely use the “Chisel test” intra-operatively to determine whether we have achieved adequate compression and rigidity after fixation of our foot and ankle fusions. This previously un-reported technique uses tools already on hand when performing an arthrodesis and takes seconds to perform.     

Response to oral β-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study

The aim of this study was to determine the efficacy of long-term oral β -carotene supplementation for correcting impaired β -carotene status in cystic fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients of fat absorption of 46-96% (median 88%) received β -carotene 0.5 mg/kg daily and were followed over a 16-month treatment period. Baseline plasma β -carotene concentrations in patients (meanSD, 0.090.06 μ mol/1) were significantly lower than those of age-matched controls (0.860.56 μ mol/1) ( p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.890.64 μ mol/1) were significantly higher ( p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and α -tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral β -carotene supplementation is effective and normalizes β -carotene status of cystic fibrosis patients without evidence of significant side effects. β -Carotene, cystic fibrosis, LDL-cholesterol, oral supplementation, retinol, α-tocopherol