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

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          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.

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          Most cited references34

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          Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon.

          This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho-associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.
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            Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury.

            Transplantation of bone marrow-derived mesenchymal stromal cells (MSCs) into the injured brain or spinal cord may provide therapeutic benefit. Several models of central nervous system (CNS) injury have been examined, including that of ischemic stroke, traumatic brain injury and traumatic spinal cord injury in rodent, primate and, more recently, human trials. Although it has been suggested that differentiation of MSCs into cells of neural lineage may occur both in vitro and in vivo, this is unlikely to be a major factor in functional recovery after brain or spinal cord injury. Other mechanisms of recovery that may play a role include neuroprotection, creation of a favorable environment for regeneration, expression of growth factors or cytokines, vascular effects or remyelination. These mechanisms are not mutually exclusive, and it is likely that more than one contribute to functional recovery. In light of the uncertainty surrounding the fate and mechanism of action of MSCs transplanted into the CNS, further preclinical studies with appropriate animal models are urgently needed to better inform the design of new clinical trials.
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              Extensive Spontaneous Plasticity of Corticospinal Projections After Primate Spinal Cord Injury

              While axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, adult rhesus monkeys underwent C7 spinal cord hemisections, with subsequent analysis of behavioral, electrophysiological and anatomical adaptations. We found remarkable spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.
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                Author and article information

                Journal
                Cell Transplant
                Cell Transplant
                CLL
                spcll
                Cell Transplantation
                SAGE Publications (Sage CA: Los Angeles, CA )
                0963-6897
                1555-3892
                05 June 2018
                June 2018
                : 27
                : 6
                : 907-915
                Affiliations
                [1 ]State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
                [2 ]The Neurosurgery & Neurology Hospital of the Affiliated Hospital of Logistics University of Chinese Armed Police Forces (CAPF), Tianjin, China
                [* ]Sai Zhang and Jianwu Dai contributed as co-corresponding authors.
                Author notes
                [*]Jianwu Dai, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100190, China. Email: jwdai@ 123456genetics.ac.cn
                [*]Sai Zhang, The Neurosurgery & Neurology Hospital of the Affiliated Hospital of Logistics University of Chinese Armed Police Forces (CAPF), 220 Chenglin Road, Tianjin, China. Email: zhangsai718@ 123456vip.126.com
                Article
                10.1177_0963689718766279
                10.1177/0963689718766279
                6050906
                29871514
                72b0fbff-7a6f-490f-a58f-85bd0f8ad102
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 5 October 2017
                : 13 February 2018
                Funding
                Funded by: the Key Research Program of the Chinese Academy of Sciences;
                Award ID: ZDRW-ZS-2016-2
                Categories
                Original Articles

                acute complete spinal cord injury,collagen scaffold,mesenchymal stem cells,motor recovery

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