Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake
organotypic slice culture, microglia, immune barrier, corticosteroid, dexamethasone, time lapse microscopy
Development of nanoparticle (NP) based therapies to promote regeneration insites of central nervous system (CNS; i.e. brain and spinal cord) pathology reliescritically on the availability of experimental models that offer biologically validpredictions of NP fate in vivo. However, there is a major lack of biological modelsthat mimic the pathological complexity of target neural sites in vivo, particularlythe responses of resident neural immune cells to NPs. Here, we have utilised apreviously developed in vitro model of traumatic spinal cord injury (based on 3-Dorganotypic slice arrays) with dynamic time lapse imaging to reveal in real-timethe acute cellular fate of NPs within injury foci. We demonstrate the utilityof our model in revealing the well documented phenomenon of avid NPsequestration by the intrinsic immune cells of the CNS (the microglia). Suchimmune sequestration is a known translational barrier to the use of NP-basedtherapeutics for neurological injury. Accordingly, we suggest that the utility ofour model in mimicking microglial sequestration behaviours offers a valuableinvestigative tool to evaluate strategies to overcome this cellular responsewithin a simple and biologically relevant experimental system, whilst reducingthe use of live animal neurological injury models for such studies.
Tsinghua University Press
Alan P. Weightman,Stuart I. Jenkins,Divya M. Chari, Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake. NanoRes.2016, 9(8): 2384–2397