Mesenchymal stem cell therapy is a novel regenerative approach for treating tendinopathy. Here, we evaluated the safety and efficacy of allogeneic adipose-derived mesenchymal stem cells (allo-ASC) in treating lateral epicondylosis (LE). Under ultrasound guidance, allo-ASCs mixed with fibrin glue were injected into the hypoechoic common extensor tendon lesions of 12 participants with chronic LE; 6 subjects each were administered 10 6 or 10 7 cells in 1 ml. Safety was evaluated at day 3 and weeks 2, 6, 12, 26, and 52 post-injection. Efficacy was assessed by measuring patients' visual analog scale (VAS) score for elbow pain, modified Mayo clinic performance index for the elbow, and by evaluating longitudinal and transverse ultrasound images of tendon defect areas after 6, 12, 26, and 52 weeks. No significant adverse effects of allo-ASC injection were observed through 52 weeks of follow-up. From baseline through 52 weeks of periodic follow-up, VAS scores progressively decreased from 66.8 6 14.5 mm to 14.8 6 13.1 mm and elbow performance scores improved from 64.0 6 13.5 to 90.6 6 5.8. Tendon defects also significantly decreased through this period. Allo-ASC therapy was thus safe and effective in improving elbow pain, performance, and structural defects for 52 weeks. This clinical study is the first to reveal therapeutic value of mesenchymal stem cell injection for treating chronic tendinopathy. STEM CELLS 2015;33:2995-3005 SIGNIFICANCE STATEMENTClinical use of mesenchymal stem cells in the treatment of tendinopathy has not been well studied because it may be related to the invasive procedures required to obtain autologous stem cells. Allogeneic stem cells may be an optimal treatment option for tendinopathy, if safety and efficacy can be conclusively demonstrated. Here, we evaluated the safety and efficacy of allogeneic adipose-derived mesenchymal stem cells in treating chronic lateral epicondylosis of 12 participants. No significant adverse effects of allogeneic stem cells were observed through 52 weeks of follow-up. Elbow pain, performance scores, and tendon defects area measured by ultrasound improved through this period. This clinical study is the first to reveal therapeutic value of mesenchymal stem cell injection for treating chronic tendinopathy.
While hemodynamic forces and intraluminal thrombus (ILT) are believed to play important roles on abdominal aortic aneurysm (AAA), it has been suggested that hemodynamic forces and ILT also interact with each other, making it a complex problem. There is, however, a pressing need to understand relationships among three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA prognosis. Hence this study used longitudinal CT scans from 14 patients and analyzed the relationship between them. Hemodynamic forces, represented by wall shear stress (WSS), were obtained from computational fluid dynamics; ILT accumulation was described by ILT thickness distribution changes between consecutives scans, and ILT accumulation and AAA expansion rates were estimated from changes in ILT and AAA volume. Results showed that, while low WSS was observed at regions where ILT accumulated, the rate at which ILT accumulated occurred at the same rate as the aneurysm expansion. Comparison between AAAs with and without thrombus showed that aneurysm with ILT recorded lower values of WSS and higher values of AAA expansion than those without thrombus. Findings suggest that low WSS may promote ILT accumulation and submit the idea that by increasing WSS levels ILT accumulation may be prevented.
[1] Space-fractional advection-dispersion models provide attractive alternatives to the classical advection-dispersion equation for model applications that exhibit early arrivals and plume skewness. This paper develops a flexible method for estimating the parameters of the fractional transport model on the basis of spatial plume snapshots or temporal breakthrough curve data. A particle-tracking approach provides error bars for the parameter estimates and a general method for model fitting and comparison via optimal weighted least squares. A simple model of concentration variance, based on the particletracking approach, identifies the optimal weights.
We present a robust microfluidic platform for the stable generation of multiple chemical gradients simultaneously using in situ self-assembly of particles in microchannels. This proposed device enables us to generate stable and reproducible diffusion-based gradients rapidly without convection flow: gradients are stabilized within 5 min and are maintained steady for several hours. Using this device, we demonstrate the dynamic position control of bacteria by introducing the sequential directional change of chemical gradients. Green Fluorescent Protein (GFP)-expressing bacterial cells, allowing quantitative monitoring, show not only tracking motion according to the directional control of chemical gradients, but also the gradual loss of sensitivity when exposed to the sequential attractants because of receptor saturation. In addition, the proposed system can be used to study the preferential chemotaxis assay of bacteria toward multiple chemical sources, since it is possible to produce multiple chemical gradients in the main chamber; aspartate induces the most preferential chemotaxis over galactose and ribose. The microfluidic device can be easily fabricated with a simple and cost effective process based on capillary pressure and evaporation for particle assembly. The assembled particles create uniform porous membranes in microchannels and its porosity can be easily controlled with different size particles. Moreover, the membrane is biocompatible and more robust than hydrogel-based porous membranes. The proposed system is expected to be a useful tool for the characterization of bacterial responses to various chemical sources, screening of bacterial cells, synthetic biology and understanding many cellular activities.
Direct current stimulation (DCS) has been known as a noninvasive method for modulating neural activity. We estimated the effects of noninvasive cutaneous DCS applied to the cervical region on corticospinal excitability and segmental sensorimotor excitability. The motor-evoked potential amplitudes and the parameters of the Hoffmann reflex were measured before, immediately after, 1 h after, and 2 h after DCS. In this study, we found that noninvasive cervical application of DCS could increase the motor-evoked potential amplitudes which reflected corticospinal tract excitability. This effect of DCS remained for 2 h after stimulation had ceased. These findings suggest DCS might be a noninvasive and effective tool for corticospinal tract excitation.
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