In Vivo Formation and Tracking of π-Peptide Nanostructures.

The photophysics associated with the self-assembly of π-peptide molecules into 1-D nanostructures has been well-established, thus revealing the creation of nanoscale electronic conduits in aqueous media. Such materials have therapeutic potential in many biomedical applications. In this work, we report the in vivo deployment of these π-peptide nanostructures in brain tissue using photothrombotic stroke as a model application. A test peptide was used for brain injections, and the nanostructures formed were visualized with electron microscopy. A new peptide bearing a low-energy fluorescence dye was prepared to facilitate direct visualization of π-peptide localization in the brain cavity by way of fluorescence microscopy. This work demonstrates feasibility for in vivo application of π-peptide nanostructures toward pressing biomedical challenges.

Promoting Brain Repair and Regeneration After Stroke: a Plea for Cell-Based Therapies.

PURPOSE OF REVIEW: After decades of hype, cell-based therapies are emerging into the clinical arena for the purposes of promoting recovery after stroke. In this review, we discuss the most recent science behind the role of cell-based therapies in ischemic stroke and the efforts to translate these therapies into human clinical trials. RECENT FINDINGS: Preclinical data support numerous beneficial effects of cell-based therapies in both small and large animal models of ischemic stroke. These benefits are driven by multifaceted mechanisms promoting brain repair through immunomodulation, trophic support, circuit reorganization, and cell replacement. Cell-based therapies offer tremendous potential for improving outcomes after stroke through multimodal support of brain repair. Based on recent clinical trials, cell-based therapies appear both feasible and safe in all phases of stroke. Ongoing translational research and clinical trials will further refine these therapies and have the potential to transform the approach to stroke recovery and rehabilitation.

Use of chelating agents to improve the resolution and consistency of cation-exchange chromatography of monoclonal antibodies.

Analytical cation-exchange chromatography (CEX) is widely used to profile the charge heterogeneity of therapeutic monoclonal antibodies (mAbs). However, the consistency of CEX profiles of a mAb can be significantly reduced by metal ion impurities from sample, mobile phase or leachates from the stainless steel components of the pumping system. In this work, we have developed a new CEX method that dynamically removes metal ions during sample analysis by incorporating the use of chelating agents (1-5mM) in HPLC mobile phases. Among four different chelating agents that were evaluated, EDTA and oxalic acid showed excellent capability of removing metal ions and provided consistent CEX chromatograms for mAb1. Furthermore, the use of oxalic acid in mobile phases not only improved the reproducibility of CEX chromatograms, but also increased the resolution of charge isoforms. Oxalic acid appears capable of binding to mAbs and reducing the positive surface charge density, resulting in a modulation of chromatographic separation. Due to this modulation effect, the CEX resolution was dependent on the concentration of the chelating agent. Optimal resolution for mAb1 was obtained with 2mM of oxalic acid. The oxalic acid modulated CEX method was shown to be capable of monitoring the degradation of mAb1. We further qualified this method according to International Committee on Harmonization (ICH) guidelines and demonstrated that the oxalic acid modulated CEX method is precise and robust at different chromatographic conditions and is suitable for use in a development and/or GMP setting.