Olfactory ensheathing cells, olfactory nerve fibroblasts and biomatrices to promote long-distance axon regrowth and functional recovery in the dorsally hemisected adult rat spinal cord

Abstract

Cellular transplantation, including olfactory ensheathing cells (OEC) and olfactory nerve fibroblasts (ONF), after experimental spinal cord injury in the rat has previously resulted in regrowth of severed corticospinal (CS) axons across small lesion gaps and partial functional recovery. In order to stimulate CS axon regrowth across large lesion gaps, we used a multifactorial transplantation strategy to create an OEC/ONF continuum in spinal cords with a 2-mm-long dorsal hemisection lesion gap. This strategy involved the use of aligned OEC/ONF-poly(D,L)-lactide biomatrix bridges within the lesion gap and OEC/ONF injections at 1 mm rostral and caudal to the lesion gap. In order to test the effects of this complete strategy, control animals only received injections with culture medium rostral and caudal to the lesion gap. Anatomically, our multifactorial intervention resulted in an enhanced presence of injured CS axons directly rostral to the lesion gap (65.0 ± 12.8% in transplanted animals versus 13.1 ± 3.9% in control animals). No regrowth of these axons was observed through the lesion site, which may be related to a lack of OEC/ONF survival on the biomatrices. Furthermore, a 10-fold increase of neurofilament-positive axon ingrowth into the lesion site as compared to untreated control animals was observed.With the use of quantitative gait analysis, a modest recovery in stride length and swing speed of the hind limbs was observed. Although multifactorial strategies may be needed to stimulate repair of large spinal lesion gaps, we conclude that the combined use of OEC/ONF and poly(D,L)-lactide biomatrices is rather limited.

Comparison of bulbar and mucosal olfactory ensheathing cells using FACS and simultaneous antigenic bivariate cell cycle analysis

“…Examples include: (a) the source of the tissue: olfactory bulb (OB), (Li et al, 1997;Ram on-Cueto et al, 1998), olfactory mucosa or lamina propria (LP); (Au and Roskams, 2002;F eron et al, 1999), (b) the age of the donor [adult, neonatal, or fetal; (Barnett and Roskams, 2008;Huang et al, 2008)], (c) the time in tissue culture (Garcia-Escudero et al, 2010a;Llamusi et al, 2010;Novikova et al, 2010), (d) whether the OECs are purified [in most studies, e.g., (Barnett and Chang, 2004;Chuah and Au, 1993)], or used as mixed primary cultures (Deumens et al, 2006;Raisman and Li, 2007;Yui et al, 2011), or cell lines (Garcia-Escudero et al, 2010b), (e) the use of growth factors (Bianco et al, 2004;Pollock et al, 1999), (f) the species: apart from the rat, other OECs have been prepared from mouse , pig (Radtke et al, 2004), dog (Ito et al, 2006), monkey (Guest et al, 2008), and human (Barnett et al, 2000;F eron et al, 1998).…”

Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke

“…Furthermore, OECs are pluripotent cells that can show Schwann cell-like properties (5). When transplanted into the demyelinated spinal cord, OECs can repair the defective myelin and restore conductance in remyelinated axons (6)(7)(8). Although much is known about OECs, few studies have focused on the characteristics of ONFs, which are flat and compact cells forming multiple layers with thin processes encircling OECs (2).…”

Neural ECM mimetics

“…They are biocompatible and biodegradable, and their mechanophysical properties (and thus the rate and timing of degradation) can be modulated to some degree (SakiyamaElbert et al, 2012). However, several studies have reported undesired effects or a lack of success that might be explained by the rate of degradation and a loss of structural support (Deumens et al, 2006;Hurtado et al, 2006).…”