Glial growth factor 2 induces proliferation and structural changes in ensheathing cells

Chuah, Mi; Cossins, J.-M; Woodhall, E; Tennent, R; Nash, Geraldine V.; West, Adrian K.

doi:10.1016/s0006-8993(99)02455-5

Cited by 31 publications

(24 citation statements)

References 38 publications

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“…These findings build on earlier studies that demonstrate that ECs contain neuregulins including GGF2 [13,52]. Taken together, the data suggest that ECs are a rich source of growth factors.…”

Section: Discussionsupporting

confidence: 88%

“…Sam ples included ECs, fibroblasts and snap frozen neonatal OBs which had intact olfactory nerve layer. Fibroblasts were isolated from neonatal rat skin according to a method that we have used in an earlier study [13].…”

Section: Reverse Transcriptase Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…These cells share phenotypic characteristics in common with Schwann cells and astrocytes [5,15,41,47] but are unique in that they can cross the transitional zone between the peripheral nervous system and CNS [17,45]. Although it is well documented that ECs express extracel lular matrix molecules such as N-CAM and laminin [22,33] that could contribute to axonal growth, few studies 204 E. Woodhall et al f Molecular Brain Research 88 (2001) [203][204][205][206][207][208][209][210][211][212][213] have shown unequivocal direct evidence that ECs syn thesize and secrete growth factors [13].…”

Section: Introductionmentioning

confidence: 99%

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

Woodhall

West

Chuah

2001

Molecular Brain Research

306

209

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Reverse Transcriptase Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Woodhall

West

Chuah

2001

Molecular Brain Research

306

209

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“…It has been shown that fibroblast growth factor 2 (FGF2) (Chuah and Teague, 1999), hepatocyte growth factor (HGF) (Yan et al, 2001b), and neuregulins (Pollock et al, 1999;Chuah et al, 2000), but not ciliary neurotrophic factor (CNTF) (Wewetzer et al, 2001), induce proliferation of bulbar ensheathing cells. It has also been demonstrated that cocktails of various growth factors, including FGF2, heregulin, forskolin, PDGF-BB, and IGF-I, promote a sustained cell division (Yan et al, 2001a;Alexander et al, 2002).…”

Section: Ensheathing Cells and Neurotrophinsmentioning

confidence: 99%

Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing cells from human nose

Bianco

Perry

Harkin

et al. 2003

Glia

122

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Several studies have demonstrated the potential of olfactory ensheathing cells for the repair of central and peripheral nerve injury. However, the majority of these studies have been performed with olfactory ensheathing cells derived from the olfactory bulbs, situated inside the skull. A more clinically relevant source of olfactory ensheathing cells is the olfactory mucosa, located in the nose. To be successful, an autologous transplant of nasal ensheathing glia would require a large number of purified cells. To address this issue, we have focused our research on three neurotrophic factors, namely nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT3). We show here that their respective receptors, TrkA, TrkB, TrkC, as well as p75(NTR) (the low affinity NGF receptor), are expressed in vitro by the nasal ensheathing cells; the three neurotrophins promote purification and proliferation of these glial cells, with an optimal concentration of 50 ng/ml; and human ensheathing cells can be easily biopsied and highly purified using a serum-free medium supplemented with NT3. This technique opens the door for clinical trials in which nasal ensheathing cells will be autotransplanted in humans suffering from nerve injury.

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“…A number of mitogens for OEG have been identified, including FGF-2, bFGF, PDGF-BB, hepatocyte growth factor, lysophosphatidic acid, BDNF, NGF, heregulin b1, and glial growth factor 2 (Alexander et al, 2002;Au and Roskams, 2003;Bianco et al, 2004;Chuah et al, 2000;Chuah and Teague, 1999;Pollock et al, 1999;Yan et al, 2001aYan et al, ,b, 2003. Of these, the latter two are of interest being members of the neuregulin (NRG) superfamily.…”

Section: Introductionmentioning

confidence: 99%

Culture conditions affect proliferative responsiveness of olfactory ensheathing glia to neuregulins

Mello

Busfield

Dunlop

et al. 2007

Glia

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Olfactory ensheathing glia (OEG) have been used to improve outcome after experimental spinal cord injury and are being trialed clinically. Their rapid proliferation in vitro is essential to optimize clinical application, with neuregulins (NRG) being potential mitogens. We examined the effects of NRG-1beta, NRG-2alpha, and NRG3 on proliferation of p75-immunopurified adult OEG. OEG were grown in serum-containing medium with added bovine pituitary extract and forskolin (added mitogens) or in serum-containing medium (no added mitogens). Cultures were switched to chemically defined medium (no added mitogens or serum), NRG added and OEG proliferation assayed using BrdU. OEG grown initially with added mitogens were not responsive to added NRGs and pre-exposure to forskolin and pituitary extract increased basal proliferation rates so that OEG no longer responded to added NRG. However, NRG promoted proliferation but only if cells were initially grown in mitogen-free medium. Primary OEG express ErbB2, ErbB3, and small levels of ErbB4 receptors; functional blocking indicates that ErbB2 and ErbB3 are the main NRG receptors utilized in the presence of NRG-1beta. The long-term stimulation of OEG proliferation by initial culture conditions raises the possibility of manipulating OEG before therapeutic transplantation.

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Glial growth factor 2 induces proliferation and structural changes in ensheathing cells

Cited by 31 publications

References 38 publications

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

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

Neurotrophin 3 promotes purification and proliferation of olfactory ensheathing cells from human nose

Culture conditions affect proliferative responsiveness of olfactory ensheathing glia to neuregulins

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