Regenerative medicine for the treatment of spinal cord injury: more than just promises? (original) (raw)
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Cell therapy for spinal cord regeneration
Advanced drug delivery reviews, 2008
This review presents a summary of the various types of cellular therapy used to treat spinal cord injury. The inhibitory environment and loss of axonal connections after spinal cord injury pose many obstacles to regenerating the lost tissue. Cellular therapy provides a means of restoring the cells lost to the injury and could potentially promote functional recovery after such injuries. A wide range of cell types have been investigated for such uses and the advantages and disadvantages of each cell type are discussed along with the research studying each cell type. Additionally, methods of delivering cells to the injury site are evaluated. Based on the current research, suggestions are given for future investigation of cellular therapies for spinal cord regeneration.
Designing Cell- and Gene-Based Regeneration Strategies To Repair the Injured Spinal Cord
Journal of Neurotrauma, 2006
There is an array of new and promising strategies being developed to improve function after spinal cord injury (SCI). The targeting of a diversity of deleterious processes within the tissue after SCI will necessitate a multi-factorial intervention, such as the combination of cell-and gene-based approaches. To ensure proper development and design of these experiments, many issues need to be addressed. It is the purpose of this review to consider the strategies involved in testing the efficacy of these new combinations to improve axonal regeneration. For cell-based therapy, issues are choosing a SCI model, the time of cell implantation, placement of cells and their subsequent migration, fluid versus solid grafts, use of agents to prevent immune rejection, and tracking of implanted cells. Grafting is also discussed in view of improving function, reducing secondary damage, bridging the injured spinal cord, supporting axonal regrowth, replacing lost neurons, facilitating myelination, and promoting axonal growth from the implant into the cord. The choice of a gene delivery system, gene-based therapies in vivo to provide chemoattractant and guidance cues, altering the intrinsic regenerative capacity of neurons, enhancing endogenous non-neuronal cell functions, and targeting the synthesis of growth inhibitory molecules are also discussed, as well as combining ex vivo gene and cell therapies.
Current Status of Spinal Cord Regenerative Therapies: A Review
Indian Journal of Neurosurgery, 2016
Spinal cord injury (SCI) is any injury resulting from an insult to the spinal cord that disrupts its major functions, either completely or incompletely, and it can be caused by both traumatic and nontraumatic events. The number of SCI patients has been continuously increasing due to increasing number of motor vehicles and average age of patients is constantly decreasing. After SCI, nerve cells located at the injured site are severely damaged and eventually die, and these dead cells are cleared away by the immune system and in turn a cavity remains. Unfortunately, till date no effective treatment strategy exists ensuring functional recovery after SCI. There is an imperative need for the development of therapies to reduce the enormous physical and financial burdens of people afflicted with SCI. The surgical treatment has been known to aid in rehabilitation, but cannot substantially improve neurologic and functional outcome after SCI. The stem cell-based therapy has been proposed as a promising treatment strategy for SCI. Many of the current strategies for treatment of SCI involve replacing the cells lost to injury with cells derived from alternative sources, such as Schwann cells, oligodendrocyte precursor cells, and neural stem cells. This review discusses the present status of various cell-based therapies, which are being used for treating SCI.
Cell Therapy in Spinal Cord Injury: a Mini- Reivew
Basic and Clinical Neuroscience, 2013
Spinal cord injury (SCI) is a debilitating disease which leads to progressive functional damages. Because of limited axonal regeneration in the central nervous system, there is no or little recovery expected in the patients. Different cellular and molecular approaches were investigated in SCI animal models. Cellular transplantation of stem cells can potentially replace damaged tissue and provide a suitable microenvironment for axons to regenerate. Here, we reviewed the last approaches applied by our colleagues and others in order to improve axonal regeneration following SCI. We used different types of stem cells via different methods. First, fetal olfactory mucosa, schwann, and bone marrow stromal cells were transplanted into the injury sites in SCI models. In later studies, was applied simultaneous transplantation of stem cells with chondroitinase ABC in SCI models with the aid of nanoparticles. Using these approaches, considerable functional recovery was observed. However, considering some challenges in stem cell therapy such as rejection, infection, and development of a new cancer, our more recent strategy was application of cytokines. We observed a significant improvement in motor function of rats when stromal derived factor-1 was used to attract innate stem cells to the injury site. In conclusion, it seems that co-transplantation of different cells accompanies with other factors like enzymes and growth factors via new delivery systems may yield better results in SCI.
Molecular Targets for Therapeutic Intervention after Spinal Cord Injury
Molecular Interventions, 2002
I n an effort to develop therapies for promoting neurological recovery after spinal cord injury, much work has been done to identify the cellular and molecular factors that control axonal regeneration within the injured central nervous system. This review summarizes the current understanding of a number of the elements within the spinal cord environment that inhibit axonal growth and outlines the factors that influence the neuron's ability to regenerate its axon after injury. Recent insights in these areas have identified important molecular pathways that are potential targets for therapeutic intervention, raising hope for victims of spinal cord injury.
Clinical and experimental advances in regeneration of spinal cord injury
Journal of tissue engineering, 2010
Spinal cord injury (SCI) is one of the major disabilities dealt with in clinical rehabilitation settings and is multifactorial in that the patients suffer from motor and sensory impairments as well as many other complications throughout their lifetimes. Many clinical trials have been documented during the last two decades to restore damaged spinal cords. However, only a few pharmacological therapies used in clinical settings which still have only limited effects on the regeneration, recovery speed, or retraining of the spinal cord. In this paper, we will introduce recent clinical trials, which performed pharmacological treatments and cell transplantations for patients with SCI, and evaluate recent in vivo studies for the regeneration of injured spinal cord, including stem-cell transplantation, application of neurotrophic factors and suppressor of inhibiting factors, development of biomaterial scaffolds and delivery systems, rehabilitation, and the combinations of these therapies to ...
Cellular treatments for spinal cord injury: the time is right for clinical trials
Neurotherapeutics, 2011
More than 1 million people in the United States live with a spinal cord injury (SCI). Despite medical advances, many patients with SCIs still experience substantial neurological disability, with loss of motor, sensory, and autonomic function. Cell therapy is ideally suited to address the multifactorial nature of the secondary events following SCI. Remarkable advances in our understanding of the pathophysiology of SCI, structural and functional magnetic resonance imaging, image-guided micro-neurosurgical techniques, and transplantable cell biology have enabled the use of cell-based regenerative techniques in the clinic. It is important to note that there are more than a dozen recently completed, ongoing, or recruiting cell therapy clinical trials for SCI that reflect the views of many key stakeholders. The field of regenerative neuroscience has reached a stage in which the clinical trials are scientifically and ethically justified. Although experimental models and analysis methods and techniques continue to evolve, no model will completely replicate the human condition. It is recognized that more work with cervical models of contusive/compressive SCI are required in parallel with clinical trials. It is also important that the clinical translation of advances made through well-established and validated experimental approaches in animal models move forward to meet the compelling needs of individuals with SCI and to advance the field of regenerative neuroscience. However, it is imperative that such efforts at translation be done in the most rigorous and informed fashion to determine safety and possible efficacy, and to provide key information to clinicians and basic scientists, which will allow improvements in regenerative techniques and the validation and refinement of existing preclinical animal models and research approaches. The field of regenerative neuroscience should not be stalled at the animal model stage, but instead the clinical trials need to be focused, safe, and ethical, backed up by a robust, translationally relevant preclinical research strategy.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-011-0076-7) contains supplementary material, which is available to authorized users.
Spinal cord injury: pathophysiology and strategies for regeneration
Orthopaedics and Trauma, 2020
Spinal cord injury (SCI) is regarded as a devastating irreversible process leading to high morbidity and dependence. The pathophysiology is complex resulting in changes in the spinal cord in the acute phase, followed by sub-acute and chronic changes. This leads to cell death, glial scar formation and the inability to regenerate. Nevertheless, many strategies for regeneration are being actively pursued, including cell therapy, drug delivery and neuromodulation. Several of these strategies are in current clinical trials. This review aims to give an overview of the current understanding of the injury process and the potential treatment strategies for SCI.
Neurospine
This is a review article examining the pharmacologic and regenerative cell therapy for spinal cord injury. A literature search during last 10 years were conducted using key words. Case reports, experimental (nonhuman) studies, papers other than English language were excluded. Up-to-date information on the pharmacologic and regenerative cell therapy for spinal cord injury was reviewed and statements were produced to reach a consensus in 2 separate consensus meeting of WFNS Spine Committee. The statements were voted and reached a consensus using Delphi method. Pharmacologic and regenerative cell therapy for spinal cord injury have long been an interest of many experimental and clinical researches. Clinical studies with methylpredinisolone have not shown clear cut benefit. Other drugs such as Rho inhibitor, minocycline, riluzole, granulocyte colony-stimulating factor have also been tried without significant benefits. Regenerative cell therapy using different types of stem cells, different inoculation techniques, and scaffolds have undergone many trials highlighting the efficacies of cells and their limitations. This review article summarizes the current knowledge on pharmacologic and regenerative cell therapy for spinal cord injury. Unfortunately, there is a need for further experimental and human trials to recommend effective pharmacologic and regenerative cell therapy.
Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells
Neurosurgical Review, 2012
Spinal cord injury (SCI) often results in significant dysfunction and disability. A series of treatments have been proposed to prevent and overcome the formation of the glial scar and inhibitory factors to axon regrowth. In the last decade, cell therapy has emerged as a new tool for several diseases of the nervous system. Stem cells act as minipumps providing trophic and immunomodulatory factors to enhance axonal growth, to modulate the environment, and to reduce neuroinflammation. This capability can be boosted by genetical manipulation to deliver trophic molecules. Different types of stem cells have been tested, according to their properties and the therapeutic aims. They differ from each other for origin, developmental stage, stage of differentiation, and fate lineage. Related to this, stem cells differentiating into neurons could be used for cell replacement, even though the feasibility that stem cells after transplantation in the adult lesioned spinal cord can differentiate into neurons, integrate within neural circuits, and emit axons reaching the muscle is quite remote. The timing of cell therapy has been variable, and may be summarized in the acute and chronic phases of disease, when stem cells interact with a completely different environment. Even though further experimental studies are needed to elucidate the mechanisms of action, the therapeutic, and the side effects of cell therapy, several clinical protocols have been tested or are under trial. Here, we report the state-of-the-art of cell therapy in SCI, in terms of feasibility, outcome, and side effects.