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      Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

      review-article
      1 , , 2
      Stem Cells International
      Hindawi

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          Abstract

          Spinal cord injury (SCI) is a distressing incident with abrupt onset of the motor as well as sensory dysfunction, and most often, the injury occurs as result of high-energy or velocity accidents as well as contact sports and falls in the elderly. The key challenges associated with nerve repair are the lack of self-repair as well as neurotrophic factors and primary and secondary neuronal apoptosis, as well as factors that prevent the regeneration of axons locally. Neurons that survive the initial traumatic damage may be lost due to pathogenic activities like neuroinflammation and apoptosis. Implanted stem cells are capable of differentiating into neural cells that replace injured cells as well as offer local neurotrophic factors that aid neuroprotection, immunomodulation, axonal sprouting, axonal regeneration, and remyelination. At the microenvironment of SCI, stem cells are capable of producing growth factors like brain-derived neurotrophic factor and nerve growth factor which triggers neuronal survival as well as axonal regrowth. Although stem cells have proven to be of therapeutic value in SCI, the major disadvantage of some of the cell types is the risk for tumorigenicity due to the contamination of undifferentiated cells prior to transplantation. Local administration of stem cells via either direct cellular injection into the spinal cord parenchyma or intrathecal administration into the subarachnoid space is currently the best transplantation modality for stem cells during SCI.

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          Most cited references265

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          Multilineage potential of adult human mesenchymal stem cells.

          Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
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            Astrocyte scar formation aids central nervous system axon regeneration.

            Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.
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              Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms

              Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                sci
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2021
                23 July 2021
                : 2021
                : 9230866
                Affiliations
                1Department of Medicine, Princefield University, P.O. Box MA128, Ho, Ghana
                2Department of Pharmacy, Ho Teaching Hospital, P.O. Box MA-374, Ho, Ghana
                Author notes

                Academic Editor: Benjamin Gantenbein

                Author information
                https://orcid.org/0000-0003-3475-0363
                Article
                10.1155/2021/9230866
                8325586
                34341666
                bba574bc-e4dd-4fe8-a922-bebab4e0fd91
                Copyright © 2021 Seidu A. Richard and Marian Sackey.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 June 2021
                : 3 July 2021
                : 17 July 2021
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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