Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability

Efficient delivery of cells to target tissues is a major problem in cell therapy. We report that enhancing delivery of mesoangioblasts leads to a complete reconstitution of downstream skeletal muscles in a mouse model of severe muscular dystrophy (α-sarcoglycan ko). Mesoangioblasts, vessel-associated stem cells, were exposed to several cytokines, among which stromal- derived factor (SDF) 1 or tumor necrosis factor (TNF) α were the most potent in enhancing transmigration in vitro and migration into dystrophic muscle in vivo. Transient expression of α4 integrins or L-selectin also increased several fold migration both in vitro and in vivo. Therefore, combined pretreatment with SDF-1 or TNF-α and expression of α4 integrin leads to massive colonization (>50%) followed by reconstitution of >80% of α-sarcoglycan–expressing fibers, with a fivefold increase in efficiency in comparison with control cells. This study defines the requirements for efficient engraftment of mesoangioblasts and offers a new potent tool to optimize future cell therapy protocols for muscular dystrophies

The GIT–PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells

Background information. Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT–PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide

A redefinição da Gestão Documental

Entre as necessidades que, atualmente, emergem em contextos informacionais tendencialmente híbridos encontra-se a da qualidade do Sistema de Gestão de Informação, à semelhança das práticas já existentes para outros sistemas de gestão organizacional. Este desafio constituiu o ponto de partida para a dissertação em Ciência da Informação (CI), realizada numa empresa de desenvolvimento de software de Gestão Documental (GD) e direcionada à realização de uma análise de domínio que sustentasse a adequação da tecnologia, a estruturação dos processos e o papel a desempenhar pelos diferentes atores. Para o efeito, partiu-se de numa abordagem teórico-metodológica direcionada à construção do Sistema de Informação Ativa e Permanente (SIAP), acrescendo-lhe o mais relevante quadro normativo de suporte à operacionalização, nomeadamente a ISO 30300, a ISO 30301, a ISO 16175 1/2/3 e a especificação MoReq2010, por forma a sustentar e alinhar a perspetiva e as necessidades do desenvolvedor de software com as do seu cliente.It is presented here a synthesis of the dissertation project that, in the context of an enterprise of development of Document Management (DM) software, aimed at the development of a domain analysis that supported the adaptation of the technology, the structuring of the processes and the role to be fulfilled by the different actors, to the needs of progressively hybrid organizational contexts and that seek to guarantee the quality of its information management system, placing it in equality with the remaining management systems. For this purpose, a theoretical and methodological approach directed to the building of the organizational Active and Permanent Information System (APIS), was taken, adding the current and most relevant standards framework directed to the operationalization support, namely the ISO 30300, the ISO 30301, the ISO 16175 1/2/3 and the MoReq2010 specification

Placental Perivascular Cells for Human Muscle Regeneration

Perivascular multipotent mesenchymal progenitors exist in a variety of tissues, including the placenta. Here, we suggest that the abundant vasculature present in the human placenta can serve as a source of myogenic cells to regenerate skeletal muscle. Chorionic villi dissected from the mid-gestation human placenta were first transplanted intact into the gastrocnemius muscles of SCID/mdx mice, where they participated in muscle regeneration by producing myofibers expressing human dystrophin and spectrin. In vitro-cultured placental villi released rapidly adhering and migratory CD146+CD34−CD45−CD56− cells of putative perivascular origin that expressed mesenchymal stem cell markers. CD146+CD34−CD45−CD56− perivascular cells isolated and purified from the placental villi by flow cytometry were indeed highly myogenic in culture, and generated dystrophin-positive myofibers, and they promoted angiogenesis after transplantation into SCID/mdx mouse muscles. These observations confirm the existence of mesenchymal progenitor cells within the walls of human blood vessels, and suggest that the richly vascularized human placenta is an abundant source of perivascular myogenic cells able to migrate within dystrophic muscle and regenerate myofibers