Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis

Clinical trials are probably the most informative experiments to help an understanding of multiple sclerosis (MS) biology. Recent successes with CD20‐depleting antibodies have focused attention towards B cell subsets as important mediators in MS. The trial of tabalumab (NTC00882999), which inhibits B cell activation factor (BAFF), is reported and reviewed and this trial is contrasted with the trial on the inhibition of a proliferation‐inducing ligand (APRIL) and BAFF using atacicept (NCT00642902). Both tabalumab and atacicept induce depletion of mature B cells and inhibit antibody formation, but they fail to deplete memory B cells and do not inhibit relapsing MS. Atacicept is reported to augment memory B cell responses and may precipitate relapse, suggesting the importance of APRIL. However, BAFF inhibition can enhance peripheral blood memory B cell responses, which was not associated with augmented relapse. Although other interpretations are possible, these data further support the hypothesis that memory B cells may be of central importance in relapsing MS, as they are the major CD20+ B cell subset expressing APRIL receptors. They also suggest that quantitative and/or qualitative differences in B cell responses or other factors, such as an immune‐regulatory effect associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors.     

Caffeic Acid–coated Nanolayer on Mineral Trioxide Aggregate Potentiates the Host Immune Responses,Angiogenesis, and Odontogenesis

IntroductionThe aim of this study was to investigate whether mineral trioxide aggregate (MTA) can be modified with caffeic acid (CA) to form caffeic acid/mineral trioxide aggregate (CAMTA) cement and to evaluate its physicochemical and biological properties as well as its capability in immune suppression and angiogenesis.MethodsMTA was immersed in trishydroxymethyl aminomethane buffer with CA to allow coating onto MTA powders. X-ray diffractometry and tensile stress-strain tests were conducted to assess for physical characteristics of CAMTA and to evaluate for successful modification of MTA. Then, the CAMTA cement was immersed in simulated body fluid to evaluate its hydroxyapatite formation capabilities and Si release profiles. In addition, RAW 264.7 cells and human dental pulp stem cells were used to evaluate CAMTA’s immunosuppressive capabilities and cell responses, respectively. hDPSCs were also used to assess CAMTA’s angiogenic capabilities.ResultsThe X-ray diffractometry results showed that CA can be successfully coated onto MTA without disrupting or losing MTA’s original structural properties, thus allowing us to retain the initial advantages of MTA. CAMTA was shown to have higher mechanical properties compared with MTA and had rougher pitted surfaces, which were hypothesized to lead to enhanced adhesion, proliferation, and secretion of angiogenic- and odontogenic-related proteins. In addition, it was found that CAMTA was able to enhance hydroxyapatite formation and immunosuppressive capabilities compared with MTA.ConclusionsCAMTA cements were found to have improved physicochemical and biological characteristics compared with their counterpart. In addition, CAMTA cements had enhanced odontogenic, angiogenic, and immunosuppressive properties compared with MTA. All of the results of this study proved that CAMTA cements could be a biomaterial for future clinical applications and tissue engineering use.     

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty‐nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow‐up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted. J. Clin. Apheresis 30:353–358, 2015. © 2015 Wiley Periodicals, Inc.     

Orthogonally oriented scaffolds with aligned fibers for engineering intestinal smooth muscle

Controlling cellular alignment is critical in engineering intestines with desired structure and function. Although previous studies have examined the directional alignment of cells on the surface (x–y plane) of parallel fibers, quantitative analysis of the cellular alignment inside implanted scaffolds with oriented fibers has not been reported. This study examined the cellular alignment in the x–z and y–z planes of scaffolds made with two layers of orthogonally oriented fibers. The cellular orientation inside implanted scaffolds was evaluated with immunofluorescence. Quantitative analysis of coherency between cell orientation and fiber direction confirmed that cells aligned along the fibers not only on the surface (x–y plane) but also inside the scaffolds (x–z & y–z planes). Our study demonstrated that two layers of orthogonally aligned scaffolds can generate the histological organization of cells similar to that of intestinal circular and longitudinal smooth muscle.