In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve

Abstract

The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T(2)-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T(2)-weighted MRI in vivo and that the T(1)-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn(2+-) enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.

Altered Retinal MicroRNA Expression Profiles in Early Diabetic Retinopathy: AnIn SilicoAnalysis

“…Furthermore, olfactory bulb development and axonogenesis demonstrated the highest ''degree'' among the down-regulated miRNAs. Olfactory bulb ensheathing cells mediate regeneration and remyelination of post-injury retinal ganglion cell axons, 29 but their function in DR, a neurodegenerative disease, 30 has not yet been reported. To our knowledge, ours is the first study to identify a potential relationship between olfactory bulbs and nerve regeneration during DR progression.…”

Current developments in cell- and biomaterial-based approaches for stroke repair

“…MRI employing superparamagnetic and paramagnetic contrast agents enables the visualization of engrafted cells as well as axonal pathways, respectively [68,[107][108][109][110], thus providing a powerful tool for image-guided cell transplantation and tracking as well as longitudinal monitoring of axon-regenerative responses to treatment [108,111]. Furthermore, multiparametric MRI, which combines complementary imaging modalities such as T2-weighted imaging, perfusion-weighted imaging (PWI), diffusion-weighted imaging (DWI) and tractography (DTI), as well as functional MRI (fMRI), enables longitudinal monitoring of cellular, molecular, anatomical, and structural integrity, as well as brain function, thus constituting a powerful tool for determining the safety and efficacy of stem cell-based therapy both in experimental models and in clinical trials.…”

Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system

“…This technique makes use of the paramagnetic properties of manganese ions (Mn 2+ ), which are taken up by neurons via L-type voltage-gated Ca 2+ channels (Narita et al 1990), enabling the imaging of regenerating RGC axons (Ryu et al 2002;Thuen et al 2005Thuen et al , 2009Chan et al 2008;Haenold et al 2012;Sandvig et al 2012;Fischer et al 2014;Sandvig and Sandvig 2014;Yang et al 2016). To visualize optic nerve regeneration, MnCl 2 is injected intravitreally, where it is taken up by the RGCs and anterogradely transported along axonal microtubule.…”