Imaging characteristics of chronic spinal cord injury identified during screening for a cell transplantation clinical trial (original) (raw)
Related papers
A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury
Journal of Neurotrauma, 2010
Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to human SCI patients. These cell types include Schwann cells, olfactory ensheathing glial cells, embryonic and adult neural stem=progenitor cells, fate-restricted neural=glial precursor cells, and bone-marrow stromal cells. Studies were included for review only if they described the transplantation of the cell substrate into an in-vivo model of traumatic SCI, induced either bluntly or sharply. Using these inclusion criteria, 162 studies were identified and reviewed in detail, emphasizing their behavioral effects (although not limiting the scope of the discussion to behavioral effects alone). Significant differences between cells of the same ''type'' exist based on the species and age of donor, as well as culture conditions and mode of delivery. Many of these studies used cell transplantations in combination with other strategies. The systematic review makes it very apparent that cells derived from rodent sources have been the most extensively studied, while only 19 studies reported the transplantation of human cells, nine of which utilized bone-marrow stromal cells. Similarly, the vast majority of studies have been conducted in rodent models of injury, and few studies have investigated cell transplantation in larger mammals or primates. With respect to the timing of intervention, nearly all of the studies reviewed were conducted with transplantations occurring subacutely and acutely, while chronic treatments were rare and often failed to yield functional benefits.
Transplantation treatment of spinal cord injury patients
2003
The minimally manipulated cells from fetal nervous and hemopoietic tissues (gestational age 16-22 weeks) were subarachnoidally implanted into 15 patients (18-52 years old) with severe consequences of traumatic spinal cord injury (SCI) at cervical or thoracic spine level. The times after SCI were from 1 month to 6 years. Each patient underwent from one to four cell transplantations (CT) with various time intervals. In 11 of 15 cases, CT was combined with an operative partial disruption of a connective tissue cyst and with implantation into a spinal cord lesion of a spinal cord fragment together with olfactory ensheathing cells. Before CT the patients showed complete motor and sensory function disorder consistent with a grade A of SCI according to Frankel classification. With CT treatment, six patients improved their neurological status from A to C grade of SCI, exhibiting incomplete restoration of both motor and sensory function. The status of other five CT-treated patients became co...
Transplantation strategies to promote repair of the injured spinal cord
The Journal of Rehabilitation Research and Development, 2003
This review describes the results of the transplantation of Schwann cells and olfactory ensheathing glia in combination with other interventions. The complete transection injury model was used to test the combination of Schwann cell bridges with methylprednisolone, neurotrophins, or olfactory ensheathing glia. The contusion injury model was used to compare Schwann cell and olfactory ensheathing glia transplantation and to examine the results of combining Schwann cell transplants with elevated levels of cyclic adenosine monophosphate. The combination strategies were more effective than cell transplantation alone. The improved regeneration response usually involved a reduction in secondary tissue loss, axonal regeneration from brainstem neurons, an increase in myelinated fibers in the transplant, the exit of regenerated fibers from the transplant into the contiguous cord, and an improvement in locomotor function.
Cellular and paracellular transplants for spinal cord injury: a review of the literature
Child's Nervous System, 2011
Background Experimental approaches to limit the spinal cord injury and to promote neurite outgrowth and improved function from a spinal cord injury have exploded in recent decades. Due to the cavitation resulting after a spinal cord injury, newer important treatment strategies have consisted of implanting scaffolds with or without cellular transplants. There are various scaffolds, as well as various different cellular transplants including stem cells at different levels of differentiation, Schwann cells and peripheral nerve implants, that have been reviewed. Also, attention has been given to different re-implantation techniques in avulsion injuries. Methods Using standard search engines, this literature is reviewed. Conclusion Cellular and paracellular transplantation for application to spinal cord injury offers promising results for those patients with spinal cord pathology.
Cell Transplantation for Spinal Cord Injury: A Systematic Review
BioMed Research International, 2013
Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studiedin vitroin detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a “bench to bedside” gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cel...
Essentials of Spinal Cord Injury Medicine, 2018
Spinal cord injury (SCI) is a distressing neurological condition that causes loss of neural tissue, with subsequent damages to neural circuitry, and loss of sensorimotor function. The SCIs have an estimated incidence rate of~80 cases per million populations. Till date, no ratified effective therapeutic strategy for SCIs exist; however, recent advancements in regenerative medicines to protect and regenerate damaged/lost neural tissues following SCIs have shown promising results in preclinical and clinical trials. Moreover, there is a greater need to fully understand underlying mechanisms following cellular transplantation that can be achieved through proper differentiation of desired cell type, and their in-vivo tracking of migration, proliferation and integration into the host system. Furthermore, techniques that can prevent teratomas formation following cellular transplantation have been reported. In addition to the ongoing comprehensive neuroregenerative and neuroprotective therapeutic strategies for SCIs, novel technologies are emerging including neuroscience-based computational and robotic rehabilitational therapies. These improved strategies in combination with cell-based therapeutic approaches are opening new avenues for future research to completely cure SCIs. Herein, we intended to review pathophysiological mechanisms following SCI, preclinical and clinical updates of cellular transplantation, the extent of success from these transplantations, associated controversies and other emerging technologies.
Anatomy & Cell Biology
SCI [1]. There is no recognized cure for treating SCI and most of the therapeutic modalities are focused on symptomatic relief [2, 3]. Approximately 90% of patients with SCI suffer from long-term motor dysfunctions and the disease related complications. These consequences impose substantial financial and emotional burdens either directly or indirectly. Currently, in most centers, pharmacotherapy has been used for treating spinal cord injuries that has minimal impact on the functional recovery and neuropathic pain symptoms. On the other hand, putting the patient on multiple medications can lead to adverse consequences in long term [4, 5]. Following a SCI, motor dysfunction will persist unless the injured region is recovered. However, neurogenesis is an uncommon phenomenon in the central nervous system (CNS)
Cellular transplantation strategies for spinal cord injury and translational neurobiology
NeuroRX, 2004
Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.
Recommended guidelines for studies of human subjects with spinal cord injury
Spinal Cord, 2005
Note: This document has taken into consideration guidelines previously recommended by the American Society for Neural Transplantation and Repair 1 for translational studies in the nervous system. Some contents of the previous document have been reproduced verbatim in this document, with permission. Goals: Research to discover therapies for spinal cord injury (SCI) has made steady progress over the last several years. Preclinical reports of neuroprotection, regeneration and functional recovery have prompted several investigators to begin planning for anticipated clinical trials, whereas other groups have already initiated such trials. The purpose of this position paper is to outline issues that should be considered in the planning, initiation and conduct of human clinical trials in SCI.
Neuroscience Letters, 2008
Several experimental studies have introduced Schwann cell transplantation as a means of recovery in animal models of spinal cord injury (SCI). The reported promising results together with the availability of autologous sources for Schwann cells indicate Schwann cell transplantation as a possible treatment for SCI. To address the safety and feasibility concerns we report 1-year follow-up of four patients aged between 22 and 43 years who had stable chronic (28-80 months) spinal cord injury at mid-thoracic level and treated with autologous Schwann cell transplantation. Purified Schwann cells used for transplantation were acquired from autologous sural nerve and cultured without the use of any specific mitogenic or growth factors. The patients were evaluated by means of American Spinal Injury Association (ASIA) criteria, sphincter, sexual function and Magnetic Resonance Imaging assessments for 1 year after transplantation. None of the patients were found to have any adverse effects indicating transfer of infection, neurological deterioration or other related clinical problems. Of the four patients, only one patient with incomplete SCI showed motor and sensory improvement 1 year after transplantation with extensive and continuous rehabilitation. All the four patients experienced transient paresthesia or increased muscle spasm after transplantation. Magnetic Resonance (MR) images of the patients did not show any visible changes or pathological findings after 1 year. This preliminary report shows that autologous Schwann cell transplantation is generally safe for the selected number of SCI patients but it does not prove beneficial effects. Further safety and outcome studies are recommended.