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

• Published in: NMR in biomedicine 2012-04, Vol.25 (4), p.620-631
• Main Authors: Sandvig, Ioanna, Thuen, Marte, Hoang, Linh, Olsen, Øystein, Sardella, Thomas CP, Brekken, Christian, Tvedt, Kåre E, Barnett, Susan C, Haraldseth, Olav, Berry, Martin, Sandvig, Axel
• Format: Article
• Language: English
• Subjects: Animals; Axons - pathology; Cell Tracking - methods; CNS injury; CNS regeneration; contrast agents; electron probe microanalysis; Female; Magnetic Resonance Imaging - methods; manganese; MEMRI; MPIO; Nerve Regeneration; Olfactory Bulb - pathology; Olfactory Bulb - transplantation; optic nerve; Optic Nerve Injuries - pathology; Optic Nerve Injuries - physiopathology; Optic Nerve Injuries - surgery; Rats; Rats, Inbred F344; Treatment Outcome; visual system
• ISSN: 0952-3480; 1099-1492; 1099-1492
• DOI: 10.1002/nbm.1778

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 T2‐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 T2‐weighted MRI in vivo and that the T1‐weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn2+−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. Copyright © 2011 John Wiley & Sons, Ltd. Regenerating retinal ganglion cell axons and MPIO‐labelled olfactory ensheathing cell (OEC) grafts were imaged by MRI in vivo. MRI detected changes in intensity profiles of the manganese‐enhanced optic nerve (ON) indicative of an OEC‐mediated regenerative response. Ultrastructural analysis confirmed increased axonal sprouting in response to OECs engrafted directly into the ON and revealed new myelin formation attributable to the OEC graft. Finally, MPIO integrity was found to be compromised beyond 40 days post‐transplantation.