Cellular transplantation strategies for spinal cord injury and translational neurobiology (original) (raw)
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Cell transplantation therapy for spinal cord injury
Nature neuroscience, 2017
Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction. Currently, there is no effective treatment for the injured spinal cord. The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord injury. However, little is known about the mechanisms through which these individual cell types promote repair and functional improvements. The five most commonly proposed mechanisms include neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration. A better understanding of the mechanisms whereby these cells promote functional improvements, as well as an appreciation of the obstacles in implementing these therapies and effectively modeling spinal cord injury, will be important to make cell transplantation a viable clinical option and may lead to the development of mo...
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.
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.
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...
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.
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.
Transplantation or Transference of Cultured Cells as a Treatment for Spinal Cord Injury
Spinal Cord Injury Therapy [Working Title], 2019
Spinal cord injury (SCI) involves damage to the spinal cord causing both structural and functional changes, which can lead to temporary or permanent alterations. Even though there have been many advances in its treatment, the results of clinical trials suggest that the current therapies are not sufficiently effective. Recently, there has been a lot of interest in regulating this harmful environment by transplanting cultured cells and boosting their antiinflammatory cytokines and growth factors production. Several types of cells have been studied for SCI therapy including, Schwann cells (SC's), olfactory ensheathing cells (OECs), choroid plexus epithelial cells (CPECs), and immune cells (ICs) (lymphocytes, dendritic cells and alternative macrophage and microglia phenotypes). These treatments have shown to be promising and in this chapter, we will review the general aspects of transplanting these cells for SCI therapy as well as the neuroprotective and regenerative responses that different types of cells have reached in different SCI models. The mesenchymal stem cells (MSC) are one of the most well studied cell types; however, they were not included in this section because they will be reviewed in another chapter of this book.
Scientific reports, 2015
Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Various animal models have been developed to mimic human SCI. Widely used animal models of SCI are complete or partial transection or experimental contusion and compression, with both bearing controversy as to which one more appropriately reproduces the human SCI functional consequences. Here we present in details the widely used procedure of complete spinal cord transection as a faithful animal model to investigate neural and functional repair of the damaged tissue by exogenous human transplanted cells. This injury model offers the advantage of complete damage to a spinal cord at a defined place and time, is relatively simple to standardize and is highly reproducible.
Experimental Neurology, 2014
To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.
Reviews in the Neurosciences, 2015
Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. The introduction of SCs into the injured spinal cord has been shown to reduce tissue loss, promote axonal regeneration, and facilitate myelination of axons for improved sensorimotor function. The pathology of spinal cord injury (SCI) comprises multiple processes characterized by extensive cell death, development of a milieu inhibitory to growth, and glial scar formation, which together limits axonal regeneration. Many studies have suggested that significant functional recovery following SCI will not be possible with a single therapeutic strategy. The use of additional approaches with SC transplantation may be needed for successful axonal regeneration and sufficient functional recovery after SCI. An example of such a combination strategy with SC transplantation has been the complementary administration of neuroprotective agents/growth factors, which improves the effect of SCs after SCI. Suspension of SCs in bioactive matrices can also enhance transplanted SC survival and increase their capacity for supporting axonal regeneration in the injured spinal cord. Inhibition of glial scar formation produces a more permissive interface between the SC transplant and host spinal cord for axonal growth. Co-transplantation of SCs and other types of cells such as olfactory ensheathing cells, bone marrow mesenchymal stromal cells, and neural stem cells can be a more effective therapy than transplantation of SCs alone following SCI. This article reviews some of the evidence supporting the combination of SC transplantation with additional strategies for SCI repair and presents a prospectus for achieving better outcomes for persons with SCI.