Dataset Information

Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells.

ABSTRACT: Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricter method combined with American Spinal Injury Association (ASIA) Impairment Scale, magnetic resonance imaging (MRI) and nerve electrophysiology. Collagen scaffolds, named NeuroRegen scaffolds, with human umbilical cord mesenchymal stem cells (MSCs) were transplanted into the injury site. During 1 year follow up, no obvious adverse symptoms related to the functional scaffolds implantation were found after treatment. The recovery of the sensory and motor functions was observed in the two patients. The sensory level expanded below the injury level, and the patients regained the sense function in bowel and bladder. The thoracic SCI patient could walk voluntary with the hip under the help of brace. The cervical SCI patient could raise his lower legs against the gravity in the wheelchair and shake his toes under control. The injury status of the two patients was improved from ASIA A complete injury to ASIA C incomplete injury. Furthermore, the improvement of sensory and motor functions was accompanied with the recovery of the interrupted neural conduction. These results showed that the supraspinal control of movements below the injury was regained by functional scaffolds implantation in the two patients who were judged as the complete injury with combined criteria, it suggested that functional scaffolds transplantation could serve as an effective treatment for acute complete SCI patients.

SUBMITTER: Xiao Z

PROVIDER: S-EPMC6050906 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells.

Xiao Zhifeng Z Tang Fengwu F Zhao Yannan Y Han Guang G Yin Na N Li Xing X Chen Bing B Han Sufang S Jiang Xianfeng X Yun Chen C Zhao Changyu C Cheng Shixiang S Zhang Sai S Dai Jianwu J

Cell transplantation 20180605 6

Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricte ...[more]

PMID: 29871514

Similar Datasets

Project description:Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial. (1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines; the animals were observed after 1 week-6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging. (2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group (n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cord tissues; the control group (n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tensor imaging showed that electrophysiological activity was recovered after the treatment. No serious complication was observed during follow-up. In contrast, the neurological functions of the patients in the control group were not improved over the follow-up period. The above data preliminarily demonstrate that the transplantation of human umbilical cord-mesenchymal stem cells on a collagen scaffold can promote the recovery of neurological function after acute spinal cord injury. In the future, these results need to be confirmed in a multicenter, randomized controlled clinical trial with a larger sample size. The clinical trial was approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on February 3, 2016 (approval No. PJHEC-2016-A8). All animal experiments were approved by the Ethics Committee of the Characteristic Medical Center of Chinese People's Armed Police Force on May 20, 2015 (approval No. PJHEC-2015-D5).

Project description:ImportanceSpinal cord infarction (SCI) is often disabling, and the diagnosis can be challenging without an inciting event (eg, aortic surgery). Patients with a spontaneous SCI are often misdiagnosed as having transverse myelitis. Diagnostic criteria for SCI are lacking, hindering clinical care and research.ObjectiveTo describe the characteristics of spontaneous SCI and propose diagnostic criteria.Design, setting, and participantsAn institution-based search tool was used to identify patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1997 to December 2017 with a spontaneous SCI. Patients provided written consent to use their records for research. Participants were 18 years and older with a diagnosis of spontaneous SCI (n = 133), and controls were selected from a database of alternative myelopathy etiologies for validation of the proposed diagnostic criteria (n = 280).Main outcomes and measuresA descriptive analysis of SCI was performed and used to propose diagnostic criteria, and the criteria were validated.ResultsOf 133 included patients with a spontaneous SCI, the median (interquartile range) age at presentation was 60 (52-69) years, and 101 (76%) had vascular risk factors. Rapid onset of severe deficits reaching nadir within 12 hours was typical (102 [77%]); some had a stuttering decline (31 [23%]). Sensory loss occurred in 126 patients (95%), selectively affecting pain/temperature in 49 (39%). Initial magnetic resonance imaging (MRI) spine results were normal in 30 patients (24%). Characteristic MRI T2-hyperintense patterns included owl eyes (82 [65%]) and pencil-like hyperintensity (50 [40%]); gadolinium enhancement (37 of 96 [39%]) was often linear and located in the anterior gray matter. Confirmatory MRI findings included diffusion-weighted imaging/apparent diffusion coefficient restriction (19 of 29 [67%]), adjacent dissection/occlusion (16 of 82 [20%]), and vertebral body infarction (11 [9%]). Cerebrospinal fluid showed mild inflammation in 7 of 89 patients (8%). Diagnostic criteria was proposed for definite, probable, and possible SCI of periprocedural and spontaneous onset. In the validation cohort (n = 280), 9 patients (3%) met criteria for possible SCI, and none met criteria for probable SCI.Conclusions and relevanceThis large series of spontaneous SCIs provides clinical, laboratory, and MRI clues to SCI diagnosis. The diagnostic criteria proposed here will aid clinicians in making the correct diagnosis and ideally improve future care for patients with SCI. The validation of these criteria supports their utility in the evaluation of acute myelopathy.

Project description:Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an "ailment not to be treated" into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope that a cure for SCI was on the horizon. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. However, recent advances in SCI research have greatly increased our understanding of the fundamental processes underlying SCI and fostered increasing optimism that these multiple treatment strategies are finally coming together to bring about a new era in which we will be able to propose encouraging therapies that will lead to appreciable improvements in SCI patients. In this review, we outline the pathophysiology of SCI that makes the spinal cord refractory to regeneration and discuss the research that has been done with cell replacement and biomaterial implantation strategies, both by itself and as a combined treatment. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI.

Dataset Information

Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells.

Publications

Significant Improvement of Acute Complete Spinal Cord Injury Patients Diagnosed by a Combined Criteria Implanted with NeuroRegen Scaffolds and Mesenchymal Stem Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets