Mechanisms of olfactory ensheathing cell-enhanced neurite outgrowth and axon regeneration after spinal cord injury

作者: Rana R. Khankan

DOI:

关键词: Olfactory ensheathing gliaNeuriteBiologyGlial scarNeuroscienceAstrocyteAxonTransplantationSpinal cord injurySpinal cord

摘要: Olfactory ensheathing cells (OECs) provide a pro-regenerative environment for the axons of olfactory receptor neurons and therefore are promising candidate cell transplantation therapy following spinal cord injury. We previously showed that OEC supports axon regeneration functional re-connectivity complete injury, yet lack an OEC-specific marker limited our ability to determine how they promoted these beneficial effects. Using both in vitro vivo models, we investigated mechanisms by which OECs mediate regeneration. enhance neurite outgrowth postnatal cortical scar-like culture model. strong evidence direct OEC-neurite alignment is critical astrocyte meningeal fibroblast inhibitory environments. also tested eGFP-OECs from transgenic rats facilitate vitro. Then short-term study, analyzed survival, migration, distribution within lesion site transected rats. found transplanted with preserve associate core, reduce presence CSPGs myelin debris, secondary tissue damage due microglial macrophage activation infiltration post-injury. Collectively, data support neuroprotective proregenerative role through modulation glial scar formation transection.

参考文章(47)
Nicolas Granger, Helen Blamires, Robin J. M. Franklin, Nick D. Jeffery, Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model Brain. ,vol. 135, pp. 3227- 3237 ,(2012) , 10.1093/BRAIN/AWS268
I. B. Wanner, M. A. Anderson, B. Song, J. Levine, A. Fernandez, Z. Gray-Thompson, Y. Ao, M. V. Sofroniew, Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. The Journal of Neuroscience. ,vol. 33, pp. 12870- 12886 ,(2013) , 10.1523/JNEUROSCI.2121-13.2013
Almudena Ramón-Cueto, Giles W. Plant, Jesus Avila, Mary Bartlett Bunge, Long-Distance Axonal Regeneration in the Transected Adult Rat Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants The Journal of Neuroscience. ,vol. 18, pp. 3803- 3815 ,(1998) , 10.1523/JNEUROSCI.18-10-03803.1998
Joanna Lipiec, Aleksandra Kulczyk, Wlodzimierz Jarmundowicz, Pawel Tabakow, Geoffrey Raisman, Wojciech Fortuna, Marcin Czyz, Juliusz Huber, Daqing Li, Pawel Szewczyk, Stefan Okurowski, Ryszard Miedzybrodzki, Bogdan Czapiga, Beata Salomon, Agnieszka Halon, Ying Li, Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplantation. ,vol. 23, pp. 1631- 1655 ,(2014) , 10.3727/096368914X685131
Michael T. Fitch, Catherine Doller, Colin K. Combs, Gary E. Landreth, Jerry Silver, Cellular and Molecular Mechanisms of Glial Scarring and Progressive Cavitation:In VivoandIn VitroAnalysis of Inflammation-Induced Secondary Injury after CNS Trauma The Journal of Neuroscience. ,vol. 19, pp. 8182- 8198 ,(1999) , 10.1523/JNEUROSCI.19-19-08182.1999
Marc D. Kubasak, Devin L. Jindrich, Hui Zhong, Aya Takeoka, Kimberly C. McFarland, Cintia Muñoz-Quiles, Roland R. Roy, V. Reggie Edgerton, Almudena Ramón-Cueto, Patricia E. Phelps, OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats Brain. ,vol. 131, pp. 264- 276 ,(2008) , 10.1093/BRAIN/AWM267
Kasper CD Roet, Elske HP Franssen, Frederik M de Bree, Anke HW Essing, Sjirk-Jan J Zijlstra, Nitish D Fagoe, Hannah M Eggink, Ruben Eggers, August B Smit, Ronald E van Kesteren, Joost Verhaagen, A Multilevel Screening Strategy Defines a Molecular Fingerprint of Proregenerative Olfactory Ensheathing Cells and Identifies SCARB2, a Protein That Improves Regenerative Sprouting of Injured Sensory Spinal Axons The Journal of Neuroscience. ,vol. 33, pp. 11116- 11135 ,(2013) , 10.1523/JNEUROSCI.1002-13.2013
Julie A. Harris, Adrian K. West, Meng Inn Chuah, Olfactory ensheathing cells: nitric oxide production and innate immunity Glia. ,vol. 57, pp. 1848- 1857 ,(2009) , 10.1002/GLIA.20899
Rosalind P Herbert, Julie Harris, Kim Pei Chong, Jamie Chapman, Adrian K West, Meng Inn Chuah, Cytokines and olfactory bulb microglia in response to bacterial challenge in the compromised primary olfactory pathway Journal of Neuroinflammation. ,vol. 9, pp. 109- 109 ,(2012) , 10.1186/1742-2094-9-109
Miranda Witheford, Kathryn Westendorf, A. Jane Roskams, Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM-dependent mechanism Glia. ,vol. 61, pp. 1873- 1889 ,(2013) , 10.1002/GLIA.22564