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Biology subjects

Barrow, M.

Publications and source records attributed to Barrow, M..

3 recordsLinked to original sources

A method for efficient, rapid, and minimally invasive implantation of individual non-functional motes with penetrating subcellular-diameter carbon fiber electrodes into rat cortex

ObjectiveDistributed arrays of wireless neural interfacing chips with 1-2 channels each, known as "neural dust", could enhance brain machine interfaces (BMIs) by removing the wired connection through the scalp and increasing biocompatibility with their submillimeter size. Although several approaches for neural dust have emerged, a procedure for implanting them in batches that builds upon the safety and performance of currently used electrodes remains to be demonstrated. ApproachHere, we demonstrate the feasibility of implanting batches of wireless motes that rest on the cortical surface with carbon fiber electrodes of subcellular diameter (6.8-8.4 {micro}m) that penetrate to a target brain depth of 1 mm without insertion aids. To simulate their implantation, we assembled more than 230 mechanically equivalent motes and affixed them to insertion tools with polyethylene glycol (PEG), a quickly dissolvable and biocompatible material. Then, we implanted mote grids of multiple configurations into rat cortex in vivo and evaluated insertion success and their arrangement on the brain surface using photos and videos captured during their implantation. Main ResultsWhen placing motes onto the insertion device, we found that they aggregated in molten PEG such that the array pitch was only 5% wider than the dimensions of the mote bases themselves (240 x 240 {micro}m). Overall, we found that motes with this arrangement could be inserted into rat cortex with a high success rate, as 171/186 (92%) motes in 4x4 (N=4) and 5x5 (N=5) square grid configurations were successfully inserted using the insertion device alone. After implantation, measurements of how much motes tilted (22{+/-}9{degrees}, [X]{+/-}S) and had been displaced relative to their original positions were smaller than those measured for devices implanted inside the brain in the literature. SignificanceCollectively, these data establish the viability of safely implementing motes with ultrasmall electrodes and epicortically-situated chips for use in future BMIs.

bioengineering↗

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

Nanoparticle contrast agents are useful tools to label stem cells and monitor the in vivo bio-distribution of labeled cells in pre-clinical models of disease. In this context, understanding the in vivo fate of the particles after injection of labelled cells is important for their eventual clinical use as well as for the interpretation of imaging results. We examined how the formulation of superparamagnetic iron oxide nanoparticles (SPIONs) impacts the labelling efficiency, magnetic characteristics and fate of the particles by comparing individual SPIONs with polyelectrolyte multilayer capsules containing SPIONs. At low labelling concentration, encapsulated SPIONs served as an efficient labelling agent for stem cells. The bio-distribution after intra-cardiac injection of labelled cells was monitored longitudinally by MRI and as an endpoint by inductively coupled plasma-optical emission spectrometry. The results suggest that, after being released from labelled cells after cell death, both formulations of particles are initially stored in liver and spleen and are not completely cleared from these organs 2 weeks post-injection.

biochemistry↗

Non-invasive imaging platform reveals a potential tumourigenicity hazard of systemically administered cells

BackgroundCell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell therapies are administered systemically, but there is little understanding of their fate, and adverse events are often under-reported. Currently, it is only possible to assess safety and fate of cell therapies in preclinical studies, specifically by monitoring animals longitudinally using multimodal imaging approaches. Here, using a suite of in vivo imaging modalities to explore the fate of a range of human and murine cells, we investigate how route of administration, cell type and host immune status affect the fate of administered cells.\n\nMethodsWe applied a unique imaging toolkit combining bioluminescence, optoacoustic and magnetic resonance imaging modalities to assess the safety of different human and murine cell types by following their biodistribution and persistence in mice following administration into the venous or arterial system. Results: Longitudinal imaging analyses (i) suggested that the intra-arterial route may be more hazardous than intravenous administration for certain cell types; (ii) revealed that the potential of a mouse mesenchymal stem/stromal cell (MSC) line to form tumours, depended on administration route and mouse strain; and (iii) indicated that clinically tested human umbilical cord (hUC)-derived MSCs can transiently and unexpectedly proliferate when administered intravenously to mice.\n\nConclusionsIn order to perform an adequate safety assessment of potential cell-based therapies, a thorough understanding of cell biodistribution and fate post administration is required. The non-invasive imaging toolbox used here can expose not only the general organ distribution of these therapies, but also a detailed view of their presence within different organs and, importantly, tumourigenic potential. Our observation that the hUC-MSCs but not the human bone marrow (hBM)-derived MSCs persisted for a period in some animals, suggests that therapies with these cells should proceed with caution.

cell biology↗