17 research outputs found
Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies
The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem
cell delivery. The deep location of the spinal cord and complex surgical access, as well as
densely packed vital structures, question the feasibility of the widespread use of multiple
spinal cord punctures to inject stem cells. Disorders characterized by disseminated
pathology are particularly appealing for the distribution of cells globally throughout the
spinal cord in a minimally invasive fashion. The intrathecal space, with access to a
relatively large surface area along the spinal cord, is an attractive route for global stem cell
delivery, and, indeed, is highly promising, but the success of this approach relies on the
ability of cells 1) to survive in the cerebrospinal fluid (CSF), 2) to adhere to the spinal cord
surface, and 3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell
suspension, however, has been insufficient and we postulate that embedding
transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this
review, we focus on practical considerations that render the intrathecal approach clinically
viable, and then discuss the characteristics of various biomaterials that are suitable to
serve as scaffolds. We also propose strategies to modulate the local microenvironment
with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we
provide an overview of imaging modalities for in vivo monitoring and characterization of
biomaterials and stem cells. This comprehensive review should serve as a guide for those
planning pre-clinical and clinical studies on intrathecal stem cell transplantation.Funds provided under the project NanoTech4ALS (ref. ENMed/0008/2015, 13/EuroNanoMed/2016), funded under the EU FP7 M-ERA.NET program, Strategmed 1/233209/12/NCBIR/2015, and NIH R01 NS091100. The FCT distinction attributed to J.M.O. under the Investigator FCT program (IF/01285/2015) is also gratefully acknowledgedinfo:eu-repo/semantics/publishedVersio
Prospective audit and feedback of piperacillin-tazobactam use in a large urban tertiary care hospital
Diversity of iron cave-dwelling mygalomorph spiders from Pará, Brazil, with description of three new species (Araneae)
Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study
Human endogenous retrovirus-like sequences.
One of the most salient features of the replication strategy used by retroviruses is the transcription of the retroviral (RNA) genome into DNA followed by integration of this DNA product into the host cell genome. The integrated viral DNA copy, termed “provirus”, can then serve as a template for the synthesis of further infectious virus particles. Stably integrated proviruses have been found to also persist in the germ line of animal cells. In this case, they have become an endogenous constituent of their host cell’s genome and are passed on as stable Mendelian genes from one generation to the next.  
Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation
The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem-loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem-loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3'-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements