Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury.
01 Sep 2013-Cell Transplantation (SAGE PublicationsSage CA: Los Angeles, CA)-Vol. 22, Iss: 9, pp 1591-1612
TL;DR: Observations at 1 year indicate that the obtaining, culture, and intraspinal transplantation of autologous olfactory ensheathing cells were safe and feasible and the significance of the neurological improvement in the transplant recipients and the extent to which the cell transplants contributed to it will require larger numbers of patients.
About: This article is published in Cell Transplantation.The article was published on 2013-09-01. It has received 234 citations till now. The article focuses on the topics: Olfactory ensheathing glia & Spinal cord injury.
Citations
More filters
TL;DR: Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types and applications are progressing in trials, some with early benefits to patients.
1,040 citations
27 Apr 2017
TL;DR: Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies.
Abstract: Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience.
980 citations
TL;DR: The advantages and disadvantages of the rat for studies of experimental spinal cord injury are discussed and the knowledge gained from such studies is summarized.
Abstract: A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.
241 citations
Cites background or methods from "Transplantation of autologous olfac..."
...Other cell-grafting strategies involve using Schwann cells (Guest et al., 1997; Williams et al., 2015; Bunge, 2016), olfactory ensheathing cells (Tabakow et al., 2013; Raisman and Li, 2007), other stem cells, embryonic CNS cells (or tissues), cells from the immune system (Rapalino et al., 1998) and…...
[...]
...The engraftment of autologous olfactory ensheathing cells cultured from the human olfactory epithelium has been tested as a treatment for chronic spinal cord injury (Tabakow et al., 2013)....
[...]
TL;DR: The ability to rescue, reactivate, and rewire spinal systems to restore function after spinal cord injury might soon be within reach.
Abstract: Spinal cord injury is currently incurable and treatment is limited to minimising secondary complications and maximising residual function by rehabilitation Improved understanding of the pathophysiology of spinal cord injury and the factors that prevent nerve and tissue repair has fuelled a move towards more ambitious experimental treatments aimed at promoting neuroprotection, axonal regeneration, and neuroplasticity By necessity, these new options are more invasive However, in view of recent advances in spinal cord injury research and demand from patients, clinicians, and the scientific community to push promising experimental treatments to the clinic, momentum and optimism exist for the translation of candidate experimental treatments to clinical spinal cord injury The ability to rescue, reactivate, and rewire spinal systems to restore function after spinal cord injury might soon be within reach
222 citations
TL;DR: The pattern of recovery suggests functional regeneration of both efferent and afferent long-distance fibers and the first clinical indication of the beneficial effects of transplanted autologous bulbar cells.
208 citations
Cites background or methods or result from "Transplantation of autologous olfac..."
...The patient met all the general and neurological criteria to be qualified for the OECtransplantation protocol as described in our recently completed phase I clinical trial (43)....
[...]
...Neurophysiological examinations included transcranial magnetic motor evoked potentials (MEPs), electroneurography (ENG) and electromyography (EMG) using the KeyPoint Diagnostic System (Medtronic, Copenhagen, Denmark), as previously described (43)....
[...]
...stereotactic cell microinjection was mounted on the operating table, as described in our previous study (43)....
[...]
...Then patient’s smell perception was tested using a scale for evaluation of smell perception we described previously (43)....
[...]
...While these studies serve to establish the safety of the procedure, there was, as in the animal studies, little (26,27,43) or no neurological improvement (6,30)....
[...]
References
More filters
TL;DR: In this paper, the authors evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury.
Abstract: Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.
2,247 citations
Journal Article•
TL;DR: The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury, that these effects occur only when the drug is given within 8 hr, and that it helps even in patients with severe spinal cord injuries.
Abstract: In 1990, the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans. The study showed that patients who received the drug within 8 hr after injury improved, whereas those who received the drug later did not. The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion, contradicting a long-held dogma that such patients would not recover. Some researchers, however, have questioned the stratification of the patient population, the use of summed neurologic change scores, and the absence of functional assessments. The stratification by injury severity and treatment time was planned a priori and based on objective criteria. Detailed analyses revealed no differences between groups attributable to stratification or randomization. While multivariate analyses of the summed neurologic scores were used, the conclusions were corroborated by other analytical approaches that did not rely on summed scores. For example, treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis, analgesia to hypalgesia, and anesthesia to hypesthesia. The treatment also significantly improved neurologic scores in lumbosacral segments, indicating that beneficial effects were not limited to segments close to the lesion site. The treatment did not significantly affect mortality or morbidity. The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury, that these effects occur only when the drug is given within 8 hr, and that it helps even in patients with severe spinal cord injuries. These conclusions have important implications for spinal cord injury care and research.
1,535 citations
TL;DR: This review briefly summarizes the current knowledge on the mechanisms involved in degeneration and tissue loss and in axonal regeneration subsequent to spinal cord lesions, particularly in mammals and humans.
Abstract: For many decades, the inability of lesioned central neurons to regrow was accepted almost as a "law of nature", and on the clinical level, spinal cord and brain lesions were seen as being irreversible. Today we are starting to understand the mechanisms of neuronal regeneration in the central nervous system and its presence in the periphery. There is now a rapid expansion in this field of neuroscience. Developmental neurobiology has produced tools and concepts that start to show their impact on regeneration research. This is particularly true for the availability of antibodies and factors and for the rapidly growing cellular and molecular understanding of crucial aspects of neurite growth, guidance, target finding, and synapse stabilization. New cell biological concepts on the mechanisms of neuron survival and death and on the interaction of inflammatory cells with the central nervous system also find their way into the field of spinal cord and brain lesions and have, indeed, led already to new therapeutic approaches. This review briefly summarizes the current knowledge on the mechanisms involved in degeneration and tissue loss and in axonal regeneration subsequent to spinal cord lesions, particularly in mammals and humans.
1,140 citations
01 Jan 1999
TL;DR: The upper cervical corticospinal tract was transected on one side in adult rats and a suspension of ensheathing cells cultured from adult rat olfactory bulb was injected into the lesion site, which induced unbranched, elongative growth of the cut cortiospinal axons.
Abstract: Injection of a suspension of cultured olfactory ensheathing cells into a unilateral lesion of the upper cervical corticospinal tract in adult rats induces regeneration of cut axons across the lesion and into the distal tract. Whether transplanted at the time of injury or 5 weeks later, the animals recover the ability to acquire a skilled directed paw reaching task on the operated side.
857 citations
TL;DR: The upper cervical corticospinal tract was transected on one side in adult rats and a suspension of ensheathing cells cultured from adult rat olfactory bulb was injected into the lesion site.
Abstract: The upper cervical corticospinal tract was transected on one side in adult rats. A suspension of ensheathing cells cultured from adult rat olfactory bulb was injected into the lesion site. This induced unbranched, elongative growth of the cut corticospinal axons. The axons grew through the transplant and continued to regenerate into the denervated caudal host tract. Rats with complete transections and no transplanted cells did not use the forepaw on the lesioned side for directed reaching. Rats in which the transplanted cells had formed a continuous bridge across the lesion exhibited directed forepaw reaching on the lesioned side.
842 citations