Improving cell transplantation after spinal cord injury: When, where and how?May 31, 2016
Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences, and unfortunately having a relatively high prevalence (250,000 patients in the USA; 80% of cases are male). One currently explored approach to restoring function after spinal cord injury is the transplantation of olfactory ensheathing cells (OECs) into the damaged area. The hope is that these will encourage the repair of damaged neurons, but does it work? And if so, how can it be optimized?
According to a systematic analysis of the literature published this week in PLOS Biology, after experimental spinal cord injury, transplanting OECs into the site of damage does indeed significantly improve locomotor performance. To reach this conclusion, Ralf Watzlawick, Jan Schwab, and their colleagues at the Ohio State University Wexner Medical Center, Charité Universtaetsmedizin Berlin and the CAMARADES consortium (Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies), analyzed 49 studies, published between 1949 and 2014, which included 62 experiments involving 1164 animals.
Restoration of function after spinal cord injury remains one of the most formidable challenges in regenerative medicine, but cell transplantation into the spinal cord represents a promising treatment strategy. OECs are considered particularly suitable for transplantation because they have been shown to be neuro-protective and to promote neuro-regeneration in different settings, and can be extracted from the patient's own nasal cavity, thereby minimizing the chances of graft rejection and avoiding the need for immunosuppressive drugs.
However, reports in the literature about the efficacy of transplantation of OECs for treatment of spinal cord injury have been contradictory. Therefore, to investigate the in vivo evidence for the efficacy of this procedure, the authors implemented a systematic review and meta-analysis of the literature. Importantly, the authors set out to explore the potential influence of variations in experimental approaches and unreported data.
"We felt that after more than two decades since the discovery that OECs elicit effects on neural plasticity in vivo, it was time to test their effects by appropriate methodology beyond reproduction", the authors argued.
The data analysed by the authors justify the use of OECs as a cellular substrate to develop and to optimize minimally invasive and secure protocols for repairing damaged spinal cord. They also identified several aspects of the cell transplantation procedure that could have a significant impact on the size of the therapeutic effect, including: the time-point of application, the use of surgical micro-dissection to "refresh" the scar tissue, the localization of transplanted cells, the number of injections, the injected volume, and the dose of cells administered.
Importantly, by using state-of-the-art statistical methods the authors also found that the impact of publication bias (due to selective failure to report results) was minimal, further supporting the translational potential of this approach.
Despite being focussing on OECs, the findings may be of more general relevance for optimizing the transplantation of other cell types after spinal cord injury.
The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies.
In your coverage please use this URL to provide access to the freely available article in PLOS Biology: http://dx.plos.org/10.1371/journal.pbio.1002468
Citation: Watzlawick R, Rind J, Sena ES, Brommer B, Zhang T, Kopp MA, et al. (2016) Olfactory Ensheathing Cell Transplantation in Experimental Spinal Cord Injury: Effect size and Reporting Bias of 62 Experimental Treatments: A Systematic Review and Meta-Analysis. PLoS Biol 14(5): e1002468. doi:10.1371/journal.pbio.1002468
Funding: RW was sponsored by the "Studienstiftung des deutschen Volkes" (#186392). JMS received funding support from the Else-Kroehner-Fresenius Foundation, the Wings-for-Life Spinal Cord Research Foundation (#60-2012), and the W.E. Hunt & C.M. Curtis Endowment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Related Spinal Cord Injury Articles:
Spinal cord patients are at higher risk for cardiovascular disease; pneumonia; life-threatening blood clots; bladder, bowel and sexual dysfunction; constipation and other gastrointestinal problems; pressure ulcers; and chronic pain, according to a report published in the journal Current Neurology and Neuroscience Reports.
Spinal cord injury (SCI) causes long-lasting damage in the spinal cord that leads to paraparesis, paraplegia, quadriplegia and other lifetime disabilities.
U-M researcher is the co-editor of a two-part series of Topics in Spinal Cord Injury Rehabilitation focused on recent research studies about health behaviors and health management in individuals with spinal cord injury.
Researchers at Lawson Health Research Institute are the first in Canada to develop clinical practice guidelines for managing neuropathic pain with patients who have experienced a spinal cord injury.
Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences.
A newly discovered pathway leading to the regeneration of central nervous system (CNS) brain cells (neurons) in a type of roundworm (C. elegans) sheds light on the adult human nervous system's ability to regenerate.
Researchers of Kazan Federal University genetically modified cord blood which managed to increase tissue sparing and numbers of regenerated axons, reduce glial scar formation and promote behavioral recovery when transplanted immediately after a rat contusion spinal cord injury.
Researchers at University of California, San Diego School of Medicine and University of British Columbia (UBC) have determined that, in mice, age diminishes ability to regenerate axons, the brain's communication wires in the spinal cord.
The research team led by Associate Professor Yukio Nishimura, National Institute for Physiological Sciences, Natural Institutes of Natural Sciences, found that the nucleus accumbens, that control motivation in the brain, activates the activity of the motor cortex of the brain, and then promotes recovery of motor function during the early stage of recovery after spinal cord injury.
Many an injury will heal, but the damaged spinal cord is notoriously recalcitrant.
Related Spinal Cord Injury Reading:
Spinal Cord Injury: Functional Rehabilitation (3rd Edition)
by Martha Freeman Somers MS PT (Author)
Compltely updated in a new edition, this unique reference is an in-depth examination of the central role of the physical therapist in rehabilitation following spinal cord injury. This book encompasses all of the elements involved in a successful rehabilitation program. It includes a basic understanding of spinal cord injuries and issues relevant to disability, as well as knowledge of the physical skills involved in functional activities and the therapeutic strategies for acquiring these skills. It also presents an approach to the cord-injured person that promotes self-respect and encourages... View Details
Spinal Cord Injury: Functional Rehabilitation (2nd Edition)
by Martha Freeman Somers (Author)
Appropriate for physical therapy students in courses covering neurorehabilitation and rehabilitation following spinal cord injury.This comprehensive text presents an in-depth examination of the central role of the physical therapist in rehabilitation following spinal cord injury. It provides updated information from clinical and basic science research, uses terminology and presents interventions consistent with published clinical practice guidelines, and includes strategies for delivering quality rehabilitative services in today's healthcare environment. View Details
Spinal Cord Injuries: Management and Rehabilitation, 1e
by Sue Ann Sisto PT MA PhD (Author), Erica Druin MPT (Author), Martha Macht Sliwinski PT MA PhD (Author)
From a hospital admittance to discharge to outpatient rehabilitation, Spinal Cord Injuries addresses the wide spectrum of rehabilitation interventions and administrative and clinical issues specific to patients with spinal cord injuries. Comprehensive coverage includes costs, life expectancies, acute care, respiratory care, documentation, goal setting, clinical treatment, complications, and activities of daily living associated with spinal cord patients. In addition to physical therapy interventions and family education components, this resource includes content on incidence, etiology,... View Details
Spinal Cord Injury
by Anders Holtz MD PhD (Author), Richard Levi MD PhD (Author)
Spinal cord injuries typically strike young, previously healthy persons, and leaves the individual with a severe, life-lasting impairment affecting all organ systems. Without adequate management, the risk of severe morbidity and mortality is very high. In contrast state-of-the-art management makes it possible for most persons with SCI to lead long, fulfilling, and autonomous lives despite neurological impairment. This book covers all medical and surgical aspects of modern SCI management from the scene of the accident through rehabilitation to the life-long follow up.
Alternative Medicine and Spinal Cord Injury
by Laurance Johnston PhD (Author)
Studies indicate that 40% of Americans use some form of alternative medicine for individuals with long-term disabilities, learning about their options is even more critical. Written by the former director of the Spinal Cord Research and Education Foundation of the PVA, this is the first book to cover alternative therapies for spinal cord injury. From acupuncture to laser-based therapies, herbal medicine, homeopathy, craniosacral therapy, magnetic healing, and more, the book empowers readers by:
Providing clear, reliable information on alternative choices to traditional health care.
... View Details
Across The Street From Hell: My Spinal Cord Injury Recovery
by Mark Anthony Hall (Author)
On his way to work the morning of August 8th 2007 Mark Hall was ejected from his vehicle during a rollover accident breaking his neck and leaving him paralyzed from the neck down. Follow him on his journey from his life as an Ironworker & Musician, through the accident, then tackling the daily obstacles of rehabilitation and his new life as a C-4, 5, 6 quadriplegic. What follows is an honest, raw and candid insight into the challenges of also being a Husband, Father to his three young daughters and his unrelenting (and successful) quest to prove wrong all the doctors and skeptics who said... View Details
Spinal Cord Injury: A Guide for Living (A Johns Hopkins Press Health Book)
by Sara Palmer PhD (Author), Kay Harris Kriegsman PhD (Author), Jeffrey B. Palmer MD (Author)
Fully updated and revised, the second edition of Spinal Cord Injury is the definitive guide for people with SCI and their families. Combining first-person accounts with up-to-date medical information, the book addresses all aspects of spinal cord injury―recovery and coping, sex and family matters, transportation and housing, employment and leisure―and reviews the challenges encountered by people with spinal cord injury throughout their lives.
The authors explain how spinal cord injury affects physical functioning and the impact of physical changes on emotions and social... View Details
Mayo Clinic Guide to Living with a Spinal Cord Injury: Moving Ahead with Your Life
by Mayo Clinic (Author)
"This indispenable guide offers a complete picture of the road to recovery, and the specifics to move ahead with your life. When possible it encourages readers to resume their favorite hobbies, participate in athletic activities and return to the workplace.
For the first time, leading medical specialists at the world-renowned Mayo Clinic offer their expert advice on everything from emotional adjustments, to skin care, to home and car modifications, to quality-of-life improvements. Easy-to-read, illustrated, and well organized, Mayo Clinic Guide to Living with A Spinal Cord Inury... View Details
Essentials of Spinal Cord Medicine
by Sunil Sabharwal MD (Author)
"From the first to the last page, this book is so full of information that as a person working in the world of spinal cord injury, I found myself in an unfamiliar situation. Never had I read a book related to my profession that I didn√åt have trouble putting down. I√åm not saying that such books are boring by any means however, they are not the captivating fictional reads that keep people up late on work nights thinking 'just one more chapter.' Essentials of Spinal Cord Medicine was that type of book for me!... Overall, I thought this book was nothing short of fantastic... it was so... View Details
Spinal Cord Injury Desk Reference: Guidelines for Life Care Planning and Case Management
by Terry L. Blackwell EdD (Author), Dr. James Schwarz Krause PhD (Author), Dr. Terry Winkler (Author), Dr. Steven A. Stiens MD (Author)
"This text provides a quick, easy-to-understand, comprehensive, evidence-based reference for health care practitioners who formulate life care plans for persons with SCI. Features that will facilitate use by practitioners includes a variety of reference materials for health care professionals who provide life care planning/case management for SCI. Life care planning/case management practitioners would best be served by utilizing this text as a source of information and a guide from which to incorporate their professional knowledge, judgment, and ethical responsibilities when working with... View Details