Olfactory ensheathing cell transplantation for spinal cord injury An 18-year bibliometric analysis based on the Web of Science

OBJECTIVE： Olfactory ensheathing cell （OEC） transplantation is a promising new approach for the treatment of spinal cord injury （SCI）, and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI. DATA SOURCE： All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A＆HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information＇s Web of Science was searched using the keywords ＂olfactory ensheathing cells＂ or ＂OECs＂ or ＂olfactory ensheathing gila＂ or ＂OEG＂ or ＂olfactory ensheathing glial cells＂ or ＂OEGs＂ and ＂spinal cord injury＂ or ＂SCI＂ or ＂spinal injury＂ or ＂spinal transection＂ for literature published from January 1898 to May 2012. DATA SELECTION： Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded. MAIN OUTCOME MEASURES： All selected literatures addressing OEC transplantation for SCI were evaluated in the following aspects： publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency.RESULTS： In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141 reviews. Thirty articles and 20 reviews, cited more than 55 times by the date the publication data were downloaded by us, can be regarded as the most classical references. The journal Experimental Neurology published the most literature （32 records）, followed by Glia. The United States had the most literature, followed by China. In addition, Yale University was the most productive institution in the world, while The Second Military Medical University contributed the most in China. The journal Experimental Neurology published the most OEC transplantation literature in the United States, while Neural Regeneration Research published the most in China. CONCLUSION： This analysis provides insight into the current state and trends in OEC transplantation for SCI research. Furthermore, we anticipate that this analysis will help encourage international cooperation and teamwork on OEC transplantation for SCI to facilitate the development of more effective treatments for SCI.

Olfactory ensheathing cell transplantation and inhibition of NogoA,NgR and RhoA expression in the damaged zone to ameliorate spinal cord injury

BACKGROUND： Olfactory ensheathing cell （OEC） transplantation promotes repair of spinal cord injury. Neural regeneration inhibits binding of the myelin protein Nogo to its receptor （NgR）, activates downstream inhibitory signal RhoA, and leads to axonal degeneration. OBJECTIVE： To determine the relationship between OECs transplantation for spinal cord injury and NogoA, NgR, and RhoA protein expression in the damaged zone. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed from September 2006 to May 2007 at the Key Laboratory of Environment and Genes in Xi＇an Jiaotong University School of Medicine, China. MATERIALS： OECs were harvested from healthy, adult, male, Sprague Dawley rats aged 6 months. Mouse anti-rat NogoA, NgR, and RheA monoclonal antibodies were utilized for detection. METHODS： A total of 40 adult Sprague Dawley rats were randomly assigned to four groups： normal, model, OECs, and DF12, with 10 animals in each group. Transverse section spinal cord injury was established in the OECs and DF12 groups, followed by injection of 1μL OECs suspension （1×10^8/mL） or equivalent DF12 medium at 1 mm above and below the injury site. MAIN OUTCOME MEASURES： Immunohistochemistry and Western blot were utilized to detect NogoA, NgR, and RhoA expression in the spinal cord injury lesions. Morphological changes were observed by argyrophilia staining, and lower extremity function of the animals was assessed using Basso, Beattie, and Bresnahan scores. RESULTS： Eight weeks following OECs transplantation, a significant increase in new axons was observed in the OECs group, and nerve fibers crossed the injury site to repair spinal cord injury. Qualitative and quantitative results from the OECs group were superior to the model and DF12 groups. At 8 weeks after transplantation, Basso, Beattie, and Bresnahan scores were significantly greater in the OECs group compared with the model and DF12 groups （P 〈 0.01）, but expression of NogoA, NgR, and RhoA protein was significantly decreased compared with the model and DF12 groups （P〈 0.05）. CONCLUSION： OEC transplantation could inhibit NogoA, NgR, and RhoA expression in spinal cord injury lesions, thereby promoting repair of spinal cord injury.

Nogo-A expression in injured spinal cord following human olfactory mucosa-derived olfactory ensheathing cells transplantation

Transplantation of olfactory bulb-derived olfactory ensheathing cells （OECs） promotes motor functional recovery in rats with acute spinal cord injury, possibly by Nogo-A expression changes at the injury site. The present study transplanted OECs derived from the olfactory mucosa （OM） of rats OM-derived OEC （OM-OEC） transplantation significantly reduced the increase of Nogo-A protein and mRNA expression caused by spinal cord injury, supporting the hypothesis that OM-OECs improve spinal cord regeneration by reducing Nogo-A expression.

Culture and purification of human fetal olfactory ensheathing cells using different attachment rates combined with intermittent NT3 nutrition

Objective：To explore a simple and pragmatic method to obtain sufficient olfactory ensheathing cells from human fetus by selective attachment of harvested cells combined with intermittent NT3 nutrition. Methods：DMEM/F12 culture solution including 10% fetal bovine serum or NT3 was used to culture olfactory ensheathing cells intermittently every 48 h. The cell state and growth rates of OECs were observed, and P75 staining was used to estimate the purity of the cells. Results：Human fetal OECs were positive with P75 immunocytochemical staining. OECs in dipolar or tripolar shape formed networks by their processes in vitro. The purity of OECs in ＂good state＂ was about 95% at 9 d and 83% on 12 d, respectively. Conclusion：The method of using different attachment rates combined with intermittent NT3 addition is a simple and effective way to culture and purify OECs.

Function of microglia and macrophages in secondary damage after spinal cord injury

Spinal cord injury （SCI） is a devastating type of neurological trauma with limited therapeutic op- portunities. The pathophysiology of SCI involves primary and secondary mechanisms of injury. Among all the secondary injury mechanisms, the inflammatory response is the major contrib- utor and results in expansion of the lesion and further loss of neurologic function. Meanwhile, the inflammation directly and indirectly dominates the outcomes of SCI, including not only pain and motor dysfunction, but also preventingneuronal regeneration. Microglia and macrophages play very important roles in secondary injury. Microglia reside in spinal parenchyma and survey the microenvironment through the signals of injury or infection. Macrophages are derived from monocytes recruited to injured sites from the peripheral circulation. Activated resident microglia and monocyte-derived macrophages induce and magnify immune and inflammatory responses not only by means of their secretory moleculesand phagocytosis, but also through their influence on astrocytes, oligodendrocytes and demyelination. In this review, we focus on the roles of mi- croglia and macrophages in secondary injury and how they contribute to the sequelae of SCI.

Chondroitinase ABC plus bone marrow mesenchymal stem cells for repair of spinal cord injury

As chondroitinase ABC can improve the hostile microenvironment and cell transplantation is proven to be effective after spinal cord injury, we hypothesized that their combination would be a more effective treatment option. At 5 days after T8 spinal cord crush injury, rats were injected with bone marrow mesenchymal stem cell suspension or chondroitinase ABC 1 mm from the edge of spinal cord damage zone. Chondroitinase ABC was first injected, and bone marrow mesenchymal stem cell suspension was injected on the next day in the combination group. At 14 days, the mean Basso, Beattie and Bresnahan score of the rats in the combination group was higher than other groups. Hematoxylin-eosin staining showed that the necrotic area was significantly reduced in the combination group compared with other groups. Glial fibrillary acidic protein-chondroitin sulfate proteoglycan double staining showed that the damage zone of astrocytic scars was significantly reduced without the cavity in the combination group. Glial fibrillary acidic protein/growth associated protein-43 double immunostaining revealed that positive fibers traversed the damage zone in the combination group. These results suggest that the combination of chondroitinase ABC and bone marrow mesenchymal stem cell transplantation contributes to the repair of spinal cord injury.