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Olfactory ensheathing cells (OECs) are a novel type of glial cell that can perform and promote many neurorestorative processes in vivo after transplant. To date, dozens of preclinical and clinical studies have confirmed that OECs have unique restoring effects in animal models and human subjects with neurological degeneration or damage, such as spinal cord injury, stroke, cerebral palsy, traumatic brain injury, and motor neuron disease (amyotrophic lateral sclerosis). To ensure the safety and effectiveness of clinical applications utilizing this type of cell, it is important to standardize cell-culture and quality-control processes. Based on a comprehensive review of published clinical studies, as well as existing methods of OEC culture and quality control currently utilized by hospitals and biomedical enterprises, the Chinese Association of Neurorestoratology has developed a set of standards for the culture and quality control of olfactory ensheathing cells for use in clinical applications. These guidelines include standardized training and management procedures for laboratory operators; standardized use and management of materials and equipment; standardized collection, culture, and proliferation of OECs obtained from fetal olfactory bulbs; standardized management for cell preservation, transport, and related safeguard measures; and the standardization of a clean environment, routine maintenance, and related tests and examinations. Our goal in publishing this set of standards is to promote the worldwide safety, effectiveness, and replicability of utilizing OECs obtained from fetal olfactory bulbs for neurorestorative clinical application.


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Neurorestorative clinical application standards for the culture and quality control of olfactory ensheathing cells

Show Author's information Juan Xiao1,2Lin Chen3Gengsheng Mao1Wenyong Gao1,2Ming Lu4Xijing He5Hongyun Huang1,2( )
Institute of Neurorestoratology, The General Hospital of Chinese People’s Armed Police Forces, Beijing, People’s Republic of China
Cell Therapy Center, Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China
Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China
Department of Neurosurgery, 163 Hospital of PLA (Second Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People’s Republic of China
Department of Orthopedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xian, Shanxi Provine, People’s Republic of China

Abstract

Olfactory ensheathing cells (OECs) are a novel type of glial cell that can perform and promote many neurorestorative processes in vivo after transplant. To date, dozens of preclinical and clinical studies have confirmed that OECs have unique restoring effects in animal models and human subjects with neurological degeneration or damage, such as spinal cord injury, stroke, cerebral palsy, traumatic brain injury, and motor neuron disease (amyotrophic lateral sclerosis). To ensure the safety and effectiveness of clinical applications utilizing this type of cell, it is important to standardize cell-culture and quality-control processes. Based on a comprehensive review of published clinical studies, as well as existing methods of OEC culture and quality control currently utilized by hospitals and biomedical enterprises, the Chinese Association of Neurorestoratology has developed a set of standards for the culture and quality control of olfactory ensheathing cells for use in clinical applications. These guidelines include standardized training and management procedures for laboratory operators; standardized use and management of materials and equipment; standardized collection, culture, and proliferation of OECs obtained from fetal olfactory bulbs; standardized management for cell preservation, transport, and related safeguard measures; and the standardization of a clean environment, routine maintenance, and related tests and examinations. Our goal in publishing this set of standards is to promote the worldwide safety, effectiveness, and replicability of utilizing OECs obtained from fetal olfactory bulbs for neurorestorative clinical application.

Keywords: neurorestoratology, cell culture, quality control, standardization, translational medicine, olfactory ensheathing glial cells, neurorestorative clinical application

References(43)

1.
Raisman G. Specialized neuroglial arrangement may explain the capacity of vomeronasal axons to reinnervate central neurons. Neuroscience. 1985;14:237–254.
2.
Doucette R. Glial influences on axonal growth in the primary olfactory system. Glia. 1990;3:433–449.
3.
Doucette R. PNS-CNS transitional zone of the first cranial nerve. J Comp Neurol. 1991;312:451–466.
4.
Ramón-Cueteo A, Nieto-Sampedro M. Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol. 1994;127:232–244.
5.
Ramón-Cueto A, Valverde F. Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties. Glia. 1995;14:163–173.
6.
Franklin RJ, Gilson JM, Franceschini IA, Barnett SC. Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS. Glia. 1996;17:217–224.
DOI
7.
Li Y, Field PM, Raisman G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science. 1997;277:2000–2002.
8.
Ramón-Cueto A, Avila J. Olfactory ensheathing glia: properties and function. Brain Res Bull. 1998;46:175–187.
9.
Ramón-Cueto A, Plant GW, Avila J, Bunge MB. Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci. 1998;18:3803–3815.
10.
Ramón-Cueto A, Cordero MI, Santos-Benito FF, Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron. 2000;25:425–435.
11.
Franklin RJ. Remyelination by transplanted olfactory ensheathing cells. Anat Rec B New Anat. 2003;271:71–76.
12.
Raisman G, Li Y. Repair of neural pathways by olfactory ensheathing cells. Nat Rev Neurosci. 2007;8:312–319.
13.
Franssen EH, de Bree FM, Verhaagen J. Olfactory ensheathing glia: their contribution to primary olfactory nervous system regeneration and their regenerative potential following transplantation into the injured spinal cord. Brain Res Rev. 2007;56:236–258.
14.
Richter MW, Roskams AJ. Olfactory ensheathing cell transplantation following spinal cord injury: hype or hope? Exp Neurol. 2008;209:353–367.
15.
Su Z, He C. Olfactory ensheathing cells: biology in neural development and regeneration. Prog Neurobiol. 2010;92:517–532.
16.
Ramón-Cueto A, Muñoz-Quiles C. Clinical application of adult olfactory bulb ensheathing glia for nervous system repair. Exp Neurol .2011;229:181–194.
17.
Higginson JR, Barnett SC. The culture of olfactory ensheathing cells (OECs): a distinct glial cell type. Exp Neurol. 2011;229:2–9.
18.
Li Y, Chen L, Zhao Y, et al. Intracranial transplant of olfactory ensheathing cells can protect both upper and lower motor neurons in amyotrophic lateral sclerosis. Cell Transplant. 2013;22:S51–S65.
19.
Wu W, Hui G, Lu H, Lv R. [Effects of different materials and culture methods on the purity of fetal olfactory ensheathing cells]. Zhonghua Shi Yan Wai Ke Za Zhi. 2004;21:841–844. Chinese.
20.
Qian LM, Zhang ZJ, Jiang P. [A novel glia: olfactory ensheathing cell]. Prog Anat Sci. 2006;12:63–66. Chinese.
21.
Huang HY. [Basic and clinical study of olfactory ensheathing cell transplantation for spinal cord injury]. Chin J Clin Rehabil. 2002;6:2027–2029. Chinese.
22.
Huang HY, Wang HM, Xiu B, et al. Preliminary report of clinical trial for olfactory ensheathing cell transplantation treating the spinal cord injury. J Navy Gen Hosp PLA. 2002;15:18–21. Chinese.
23.
Huang HY, Chen L, Wang HM, et al. Influence of patients’ age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chin Med J (Engl). 2003;116:1488–1491.
24.
Huang H, Chen L, Xi H, et al. Fetal olfactory ensheathing cells transplantation in amyotrophic lateral sclerosis patients: a controlled pilot study. Clin Transplant. 2008;22:710–718.
25.
Mackay-Sim A, Féron F, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain. 2008;131:2376–2386.
26.
Huang HY, Chen L, Xi HT, et al. [Olfactory ensheathing cells transplantation for central nervous system diseases in 1,255 patients]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009:23:14–20. Chinese.
27.
Chen L, Huang H, Xi H, et al. Intracranial transplant of olfactory ensheathing cells in children and adolescents with cerebral palsy: a randomized controlled clinical trial. Cell Transplant. 2010;19:185–191.
28.
Huang H, Xi H, Chen L, Zhang F, Liu Y. Long-term outcome of olfactory ensheathing cell therapy for patients with complete chronic spinal cord injury. Cell Transplant. 2012;21:S23–S31.
29.
Chen L, Chen D, Xi H, et al. Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: benefits from multiple transplantations. Cell Transplant. 2012;21:S65–S77.
30.
Rao Y, Zhu W, Guo Y, et al. Long-term outcome of olfactory ensheathing cell transplantation in six patients with chronic complete spinal cord injury. Cell Transplant. 2013;22:S21–S25.
31.
Tabakow P, Jarmundowicz W, Czapiga B, et al. Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant. 2013;22:1591–1612.
32.
Chen L, Xi H, Huang H, et al. Multiple cell transplantation based on an intraparenchymal approach for patients with chronic phase stroke. Cell Transplant. 2013;22:S83–S91.
33.
Xi H, Chen L, Huang H, et al. Preliminary report of multiple cell therapy for patients with multiple system atrophy. Cell Transplant. 2013;22:S93–S99.
34.
Tabakow P, Raisman G, Fortuna W, et al. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 2014;23:1631–1655.
35.
Chen L, Huang H, Xi H, et al. A prospective randomized double-blind clinical trial using a combination of olfactory ensheathing cells and Schwann cells for the treatment of chronic complete spinal cord injuries. Cell Transplant. 2014;23:S35–S44.
36.
Wang S, Lu J, Li YA, et al. Autologous olfactory lamina propria transplantation for chronic spinal cord injury: three-year follow-up outcomes from a prospective double-blinded clinical trial. Cell Transplant. 2016;25:141–157.
37.
Ren YS, Huang HY, Chen L, et al. The primary culture for human embryonic olfactory ensheathing cells of olfactory bulb. Prog Anat Sci. 2010;16:97–100. Chinese.
38.
Ren YS, Tian GZ, Wang HM, Huang HY, Chen L. Quality specification of human embryo olfactory ensheathing cells from olfactory bulb. J Clin Rehabil Tissue Eng Res. 2008;12:3156–3157. Chinese.
39.
Jiang XR, Xiao J, Ren YS, et al. The influence of 4 degree centigrade concervation [sic] on cells activity of rats’ olfactory bulbs derived olfactory ensheathing cells. Prog Anat Sci. 2011;17:424–427. Chinese.
40.
International Association of Neurorestoratology [homepage on the Internet]. Available from: http://www.ianr.org.cn/zcfg. Accessed September 8, 2017. Chinese.
41.
Chinese Medical Association of Neurorestoratology Professional Committee, Chinese Branch of International Association of Neurorestoratology. Chinese clinical application guideline of neurorestorative cell therapy (version 2015). Chin J Cell Stem Cell. 2016;6:1–7. Chinese.
42.
Huang H, Chen L, Zou Q, et al. Clinical cell therapy guidelines for neurorestoration (China version 2016). J Neurorestoratol. 2017;5:39–46.
43.
Gobbel GT, Kondziolka D, Fellows-Mayle W, Uram M. Cellular transplantation for the nervous system: impact of time after preparation on cell viability and survival. J Neurosurg. 2010;113:666–672.
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Published: 22 September 2017
Issue date: December 2017

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© 2017 The Author(s).

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We sincerely thank Professor Priscilla Song (Washington University in St Louis) for her editorial assistance in polishing this manuscript.

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