Human embryonic stem cell-derived neural precursor transplants in collagen scaffolds promote recovery in injured rat spinal cord

Background aimsSeveral studies have reported functional improvement after transplantation of in vivo-derived neural progenitor cells (NPC) into injured spinal cord. However, the potential of human embryonic stem cell-derived NPC (hESC-NPC) as a tool for cell replacement of spinal cord injury (SCI) should be considered.MethodsWe report on the generation of NPC as neural-like tubes in adherent and feeder-free hESC using a defined media supplemented with growth factors, and their transplantation in collagen scaffolds in adult rats subjected to midline lateral hemisection SCI.ResultshESC-NPC were highly expressed molecular features of NPC such as Nestin, Sox1 and Pax6. Furthermore, these cells exhibited the multipotential characteristic of differentiating into neurons and glials in vitro. Implantation of xenografted hESC-NPC into the spinal cord with collagen scaffold improved the recovery of hindlimb locomotor function and sensory responses in an adult rat model of SCI. Analysis of transplanted cells showed migration toward the spinal cord and both neural and glial differentiation in vivo.ConclusionsThese findings show that transplantation of hESC-NPC in collagen scaffolds into an injured spinal cord may provide a new approach to SCI.     

Construction and functional characterization of a fully human anti-CD19 chimeric antigen receptor (huCAR)-expressing primary human T cells

Although remarkable results have been attained by adoptively transferring T cells expressing fully murine and/or humanized anti-CD19 chimeric antigen receptors (CARs) to treat B cell malignancies, evidence of human anti-mouse immune responses against CARs provides a rationale for the development of less immunogenic CARs. By developing a fully human CAR (huCAR), these human anti-mouse immune responses are likely eliminated. This, perhaps, not only increases the persistence of anti-CD19 CAR T cells—thereby reducing the risk of tumor relapse—but also facilitates administration of multiple, temporally separated doses of CAR T cells to the same recipient. To these ends, we have designed and constructed a second-generation fully human anti-CD19 CAR (or huCAR19) containing a fully human single-chain variable fragment (ScFv) fused with a CD8a hinge, a 4-1BB transmembrane domain and intracellular T cell signaling domains of 4-1BB and CD3z. T cells expressing this CAR specifically recognized and lysed CD19⁺ target cells produced cytokines and proliferated in vitro. Moreover, cell volume data revealed that our huCAR construct cannot induce antigen-independent tonic signaling in the absence of cognate antigen. Considering our results, our anti-CD19 huCAR may overcome issues of transgene immunogenicity that plague trials utilizing CARs containing mouse-derived ScFvs. These results suggest that this huCAR19 be safely and effectively applied for adaptive T cell immunotherapy in clinical practice.     

Deformation and fragmentation of human red blood cells in turbulent shear flow.

By means of glutaraldehyde fixation, human erythrocytes are "frozen" while suspended in turbulent shear flow. As the shearing is increased in steps from 100 to 2,500 dyn/cm2, the deformed cells evolve gradually toward a smooth ellipsoidal shape. At stresses above 2,500 dyn/cm2, approximately, fragmentation of the cells occurs with a concomitant increase in free hemoglobin content of the suspending medium. The photographic evidence suggests that the cells rupture in tension in the bulk flow.     

烟草黄矮双生病毒中双向启动子的活性及其调节控制

将烟草黄矮双生病毒（ＴｏｂＹＤＶ）中双向启动子的区域,以不同长度的片段和方向插入启动子分析载体ｐＧ１,与ＧＵＳ报道基因和ＮＯＳ终止子融合。同时,将各个ＴｏｂＹＤＶ读码框区域插入表达载体ｐＡＲＴ７中,置于ＣａＭＶ３５Ｓ启动子和ＯＣＳ终止子之间。用电穿孔法将各种启动子构建物个别地或者与读码框构建物成对地导入烟草和玉米原生质体,以考察ＴｏｂＹＤＶ启动子控制下ＧＵＳ基因瞬间表达的活性,以及ＴｏｂＹＤＶ的读