Transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury: A Web of Science-based literature analysis

Abstract

Objective: To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. Data Retrieval: We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. Selection Criteria: Inclusion criteria: (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. Main Outcome Measures: (1) Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. Results: This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Glia. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were mostly in the USA and Canada as well. Those publishing on the use of olfactory ensheathing cells were mostly in the UK, the USA and Canada. Conclusion: On the basis of the large number of studies around the world, cell transplantation has proven to be the most promising therapeutic approach for spinal cord injury. Research Highlights

1. We performed a bibliometric analysis of published studies on neural stem cells, Schwann cells and olfactory ensheathing cells to repair spinal cord injury from 2002 to 2011 retrieved from the Web of Science.
2. We analyzed the publication year, journals, institutions and highly cited papers.

INTRODUCTION

Spinal cord injury is severe trauma of the central nervous system. Over the years, various methods have been used to treat spinal cord injury, including surgical anastomosis, surgical decompression, omental transplantation, drug treatment, partial freeze, physical rehabilitation, and the application of enzyme preparations to reduce or eliminate connective tissue scarring. Although these methods can alleviate the pathological changes associated with spinal cord injury, they have been unable to provide satisfactory clinical improvement[1],[2]. Recently, cell transplantation has become a hot therapeutic approach for the treatment of spinal cord injury.

Neural stem cells are pluripotent stem cells that have the potential to self-replicate and undergo multi-directional differentiation. Neural stem cells not only promote neuroregeneration, but can also be used in gene therapy for nervous system diseases by undergoing genetic modification to express exogenous neurotransmitters, neurotrophic factors and metabolic enzymes. These cells help demyelinated nerve fibers and newborn nerve fibers undergo myelination to maintain their integrity[3],[4].

Schwann cells are glial cells in the peripheral nervous system. After spinal cord injury, Schwann cells can migrate to the site of injury. These cells can secrete a variety of neurotrophic factors to promote neuronal survival and encourage neurite outgrowth and functional synapse formation. Furthermore, Schwann cells can produce extracellular matrix components and cell adhesion molecules. These molecules promote neurite outgrowth and serve as a scaffold for migrating neurons. They can also fill necrotic voids and inhibit glial scar formation to improve the microenvironment[5],[6].

Olfactory ensheathing cells are the only glial cells present in both the peripheral and central nervous system. They exhibit characteristics of both astrocytes and Schwann cells. Olfactory ensheathing cells can express many molecules related to cell adhesion and neurite outgrowth, and they secrete a multitude of neurotrophic factors to provide a good environment for nerve regeneration. Olfactory ensheathing cells can pass through the glial scar to provide the appropriate conditions for axonal regeneration[7],[8].

In this study, we analyzed research trends among cell transplantation studies using these three different cell types for spinal cord injury based on a bibliometric analysis of publications indexed in the Web of Science and published from 2002 to 2011.

DATA SOURCES AND METHODOLOGY

Data retrieval

This study used bibliometric analyses to quantitatively and qualitatively investigate research trends in studies of transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. We searched the Web of Science, a database of research publications and citations, selected and evaluated by the Institute for Scientific Information in Philadelphia, PA, USA, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell to find articles on the use of neural stem cells, Schwann cells or olfactory ensheathing cells, respectively, for the repair of spinal cord injury. We limited the period of publication from 2002 to 2011 and compiled a bibliography of all articles related to these cells. We downloaded the data on August 16, 2012.

Inclusion criteria

Inclusion criteria were as follows: (1) published peer-reviewed articles on any of the three types of cells, including original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items, indexed in the Web of Science; (2) year of publication 2002-2011; and (3) citation database was Science Citation Index Expanded.

Exclusion criteria

We excluded articles that required manual searching or telephone access, documents that were not published in the public domain, and several corrected papers.

Outcomes for all articles referring to the three kinds of cells for the repair of spinal cord injury were assessed using the following criteria: (1) annual publication output on neural stem cells; (2) distribution by journal on neural stem cells; (3) distribution by institution on neural stem cells; (4) most-cited articles from 2002 to 2011 on neural stem cells; (5) annual publication output on Schwann cells; (6) distribution by journal on Schwann cells; (7) distribution by institution on Schwann cells; (8) most-cited articles from 2002 to 2011 on Schwann cells; (9) annual publication output on olfactory ensheathing cells; (10) distribution by journal on olfactory ensheathing cells; (11) distribution by institution on olfactory ensheathing cells; and (12) most-cited articles from 2002 to 2011 on olfactory ensheathing cells.

RESULTS

Annual publication output relating to the use of neural stem cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 537 publications from 2002 to 2011 on the use of neural stem cells to repair spinal cord injury were retrieved from the Web of Science. The number of relevant publications increased over the 10-year period. Only 14 papers were published and included in the Web of Science in 2002, but the number of published papers had increased to 101 in 2011. While the number of publications increased over this period, there was a slight decrease in 2010 (compared with 2009) [Figure 1].{Figure 1}

Distribution of output by journal for publications on the use of neural stem cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

Journal of Neurotrauma published 23 papers, followed by Journal of Neuroscience Research, Experimental Neurology and Cell Transplantation, which published 21, 19 and 18 papers, respectively [Table 1].{Table 1}

Distribution of output by institution for publications on the use of neural stem cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 537 articles were analyzed according to institution. Keio University in Japan and Harvard University in the USA were the most prolific research institutes [Table 2]. Four of the top 10 research institutes publishing in this field were in the USA, two were in Canada, and one institute each was in Japan, Sweden, China and Korea.{Table 2}

Highly cited papers on the use of neural stem cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 537 papers on the use of neural stem cells to repair spinal cord injury were cited in the Web of Science from 2002 to 2011. “Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells”, published in 2002 by the journal Proceedings of the National Academy of Sciences of the United States of America[9], was cited 418 times, which was more times than any other papers [Table 3].{Table 3}

Of the 10 most-cited papers, two were published in Proceedings of the National Academy of Sciences of the United States of America, and the remaining eight papers were published in eight different journals. Of these 10 most-cited papers, four were published in 2005, two in 2002, and one each in 2003, 2004, 2006 and 2009.

Annual publication output relating to the use of Schwann cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011 [Figure 2]{Figure 2}

A total of 541 papers on the use of Schwann cells to repair spinal cord injury, published from 2002 to 2011, were retrieved from the Web of Science. The number of relevant publications increased over the 10-year period; 31 papers were published and included in the Web of Science in 2002, and the number of published papers increased to 104 in 2011. However, the number of papers published decreased slightly in 2003, 2005, 2007, 2008 and 2010.

Distribution of output by journal for publications on the use of Schwann cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011 [Table 4]{Table 4}

Experimental Neurology published 47 papers, followed by Journal of Neurotrauma, Glia and Journal of Neuroscience, which published 40, 25 and 24 papers, respectively [Table 4].

Distribution of output by institution for publications on the use of Schwann cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 541 articles were analyzed by institution. University of California system and University of Miami in the USA were the most prolific research institutes [Table 5]. Five of the top 10 research institutes publishing in this field were in the USA, three were in Canada, and one institute each was in Germany and China.{Table 5}

Highly cited papers on the use of Schwann cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 541 papers on the use of Schwann cells to repair spinal cord injury, published from 2002 to 2011 were cited in the Web of Science. “cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury”, published in 2004 by the journal Nature Medicine [19], was cited 323 times, which was more than any other paper. Of the 10 most-cited papers, four were published in Journal of Neuroscience, and the remaining six papers were published in six different journals. Of these 10 most-cited papers, four were published in 2005, three in 2002, and one each in 2003, 2004 and 2007 [Table 6].{Table 6}

Annual publication output relating to the use of olfactory ensheathing cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 351 publications on the use of olfactory ensheathing cells to repair spinal cord injury, published from 2002 to 2011, were retrieved from the Web of Science. The number of relevant publications increased over the 10-year period; 10 papers were published and included in the Web of Science in 2002, but the number of published papers increased to 63 in 2011. However, the number of papers published slightly decreased in 2008 and 2009 [Figure 3].{Figure 3}

Distribution of output by journal for publications on the use of olfactory ensheathing cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

Experimental Neurology published 26 papers, followed by Glia, Journal of Neurotrauma and Neural Regeneration Research, which published 16, 16 and 12 papers, respectively [Table 7].{Table 7}

Distribution of output by institution for publications on the use of olfactory ensheathing cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011

A total of 351 articles were analyzed by institution. University of British Columbia in Canada and Yale University in the USA were the most prolific research institutes [Table 8].{Table 8}

Three of the top 11 research institutes publishing in this field were in the UK, two each were in the USA and Canada, and one institute each was in Germany, Australia, China and France.

Highly cited papers on the use of olfactory ensheathing cells to repair spinal cord injury indexed in the Web of Science and published from 2002 to 2011 [Table 9]{Table 9}

A total of 351 papers on the use of olfactory ensheathing cells to repair spinal cord injury, published from 2002 to 2011, were cited in the Web of Science. “Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells”, published in 2002 by the journal Proceedings of the National Academy of Sciences of the United States of America[9], was cited 418 times, which was more than any other paper. Of the 10 most-cited papers, two were published in Brain, and the remaining eight papers were published in eight different journals. Of these 10 most-cited papers, three each were published in 2002 and 2006, and one each in 2003, 2004, 2005 and 2007.

DISCUSSION

A bibliometric analysis, based on Web of Science publications, identified several research trends over the past 10 years in studies on the use of neural stem cells, Schwann cells and olfactory ensheathing cells to repair spinal cord injury. The number of publications increased over the 10-year period, which indicates that these three types of cells became increasingly important for treating spinal cord injury. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Glia. Research institutes publishing on the use of neural stem cells to repair spinal cord injury are mostly in the USA and Canada. Those publishing on the use of Schwann cells to repair spinal cord injury were mostly in the USA and Canada too.

Those publishing on the use of olfactory ensheathing cells to repair spinal cord injury were mostly in the UK, the USA and Canada.

From our analysis, we believe that spinal cord regeneration is a complex process limited by multiple factors. Future research may focus on the following aspects: (1) Cell transplantation combined with genetic engineering techniques to eliminate the disadvantage of cell transplantation for spinal cord injury; (2) Cell transplantation combined with tissue engineering to replace spinal cord defects with carrier or scaffolding material to provide sites for transplanted cells to grow and differentiate; (3) Multiple types of cells jointly transplanted to create a suitable microenvironment for spinal cord repair; (4) Identification of a suitable source of seed cells to overcome problems related to cell differentiation, immunogenicity and regulation in transplantation. Researchers have obtained promising results in animal experiments[34]. We believe that with further investigation, researchers will make substantial breakthroughs in the treatment of spinal cord injury.