Bianco John I, Perry Chris, Harkin Damien G, Mackay-Sim Alan, Féron François
Centre for Molecular Neurobiology, School of Biomolecular and Biomedical Science, Griffith University, Nathan, Queensland 4111, Australia.
Glia. 2004 Jan 15;45(2):111-23. doi: 10.1002/glia.10298.
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.
多项研究已证明嗅鞘细胞在修复中枢和周围神经损伤方面的潜力。然而,这些研究大多使用的是源自位于颅骨内的嗅球的嗅鞘细胞。嗅鞘细胞更具临床相关性的来源是位于鼻腔内的嗅黏膜。要成功进行鼻鞘胶质细胞的自体移植,需要大量纯化的细胞。为了解决这个问题,我们将研究重点集中在三种神经营养因子上,即神经生长因子(NGF)、脑源性神经营养因子(BDNF)和神经营养素3(NT3)。我们在此表明,它们各自的受体TrkA、TrkB、TrkC以及p75(NTR)(低亲和力NGF受体)在体外由鼻鞘细胞表达;这三种神经营养因子促进这些胶质细胞的纯化和增殖,最佳浓度为50 ng/ml;并且使用补充有NT3的无血清培养基可以轻松地对人鞘细胞进行活检和高度纯化。这项技术为临床试验打开了大门,在这些试验中,鼻鞘细胞将被自体移植到神经损伤患者体内。