Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord

Abstract

Olfactory ensheathing cells (OECs), which have properties of both astrocytes and Schwann cells, can remyelinate axons with a Schwann cell-like pattern of myelin. In this study the pattern and extent of remyelination and the electrophysiological properties of dorsal column axons were characterized after transplantation of OECs into a demyelinated rat spinal cord lesion. Dorsal columns of adult rat spinal cords were demyelinated by x-ray irradiation and focal injections of ethidium bromide. Cell suspensions of acutely dissociated OECs from neonatal rats were injected into the lesion 6 d after x-ray irradiation. At 21-25 d after transplantation of OECs, the spinal cords were maintained in an in vitro recording chamber to study the conduction properties of the axons. The remyelinated axons displayed improved conduction velocity and frequency-response properties, and action potentials were conducted a greater distance into the lesion, suggesting that conduction block was overcome. Quantitative histological analysis revealed remyelinated axons near and remote from the cell injection site, indicating extensive migration of OECs within the lesion. These data support the conclusion that transplantation of neonatal OECs results in quantitatively extensive and functional remyelination of demyelinated dorsal column axons.

Cell Therapy for Multiple Sclerosis

“…These cells are unique in that they continue to arise in the olfactory epithelium from which they can migrate to the olfactory bulb throughout life [232][233][234]. Rodent and human OECs generate Schwann-cell-like myelin and improve conduction properties when transplanted to areas of demyelination in the brain or spinal cord [227,233,[235][236][237][238][239][240]. OECs also have the capacity to promote axonal growth [241] and to secrete neurotrophic molecules [242,243].…”

Remyelination of the spinal cord following intravenous delivery of bone marrow cells

“…Following a second centrifugation (2,000 rpm, 15 min), the cells were collected in saline solution. Schwann cells and olfactory ensheathing cells were prepared from adult rats as previously described by Honmou et al (1996) and Imaizumi et al (1998), respectively.…”

Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

“…While the precise mechanism of this functional recovery is not fully understood, several mechanisms have been suggested including remyelination (Devon and Doucette, 1992;Franklin et al, 1996;Imaizumi et al, 1998;Sasaki et al, 2004), long axon tract regeneration (Li et al, 1997;Ramon-Cueto et al, 2000;, axonal sparing (Plant et al, 2002) and plasticity associated with novel polysynaptic pathways (Keyvan-Fouladi et al, 2002;Bareyre et al, 2004). In addition, recruitment of endogenous SCs (Takami et al, 2002;Boyd et al, 2004;Ramer et al, 2004) and remote inhibition of apoptosis of motor cortical neurons (Sasaki et al, 2006a) have been suggested to contribute to improvement in functional outcome in injured spinal cord after OEC transplantation.…”