Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors

Abstract

In the primary olfactory pathway axons of olfactory neurons (ONs) are accompanied by ensheathing cells (ECs) as the fibres course towards the olfactory bulb. Ensheathing cells are thought to play an important role in promoting and guiding olfactory axons to their appropriate target. In recent years, studies have shown that transplants of ECs into lesions in the central nervous system (CNS) are able to stimulate the growth ofaxons and in some cases restore functional connections. In an attempt to identify a possible mechanism underlying EC support for olfactory nerve growth and CNS axonal regeneration, this study investigated the production of growth factors and expression of corresponding receptors by these cells. Three techniques immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess growth factor expression in cultured ECs. Immunohistochemistry showed that ECs expressed nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF). ELISA confirmed the intracellular presence of NGF and BDNF and showed that, compared to BDNF, about seven times as much NGF was secreted by ECs. RT-PCR analysis demonstrated expression of mRNA for NGF, BDNF, GDNF and neurturin (NTN). In addition, ECs also expressed the receptors trkB, GFRa-1 and GFRa-2. The results of the experiments show that ECs express a number of growth factors and that BDNF in particular could act both in a paracrine and autocrine manner.

Ensheathing Cells and Methylprednisolone Promote Axonal Regeneration and Functional Recovery in the Lesioned Adult Rat Spinal Cord

“…A subsequent study (Kafitz and Greer, 1999) demonstrated that olfactory receptor cell extension in culture was facilitated by exposure to media conditioned by ECs, indicating that the neurite growthpromoting properties of ECs were, at least in part, mediated by diffusible factors. Data supporting this idea was reported earlier this year, when cultured ECs were found to express nerve growth factor, brain-derived neurotrophic factor, and glial cell linederived neurotrophic factor (Woodhall et al, 2001).…”

Cell Therapy for Multiple Sclerosis

“…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]. Thus, the relative availability of these cells, their apparent myelinating properties and their trophic effect on axonal growth make them another promising candidate for autologous therapeutic transplantation.…”

Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells

“…35 Possible mechanisms of rapid neurological changes Trophic effects due to factors released from the transplanted cells could cause angiogenesis, 36 neuronal plasticity, or influence synaptic conduction. 37 Neonatal rodent OECs release nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) into culture media 38 but adult rodent OECs release negligible quantities of BNDF into culture media. 39 Exogenous NGF and BDNF have been shown to enhance glutamatergic neurotransmission in the brain 40 by both pre-and postsynaptic mechanisms 41 and to induce formation of new synapses.…”