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      Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

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          Abstract

          Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

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          Most cited references57

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          Immunomodulation by mesenchymal stem cells and clinical experience.

          Mesenchymal stem cells (MSCs) from adult marrow can differentiate in vitro and in vivo into various cell types, such as bone, fat and cartilage. MSCs preferentially home to damaged tissue and may have therapeutic potential. In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders.
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            Evaluation and management of peripheral nerve injury.

            Common etiologies of acute traumatic peripheral nerve injury (TPNI) include penetrating injury, crush, stretch, and ischemia. Management of TPNI requires familiarity with the relevant anatomy, pathology, pathophysiology, and the surgical principles, approaches and concerns. Surgical repair of TPNI is done at varying time intervals after the injury, and there are a number of considerations in deciding whether and when to operate. In neurapraxia, the compound muscle and nerve action potentials on stimulating distal to the lesion are maintained indefinitely; stimulation above the lesion reveals partial or complete conduction block. The picture in axonotmesis and neurotmesis depends on the time since injury. The optimal timing for an electrodiagnostic study depends upon the clinical question being asked. Although conventional teaching usually holds that an electrodiagnostic study should not be done until about 3 weeks after the injury, in fact a great deal of important information can be obtained by studies done in the first week. Proximal nerve injuries are problematic because the long distance makes it difficult to reinnervate distal muscles before irreversible changes occur. Decision making regarding exploration must occur more quickly, and exploration using intraoperative nerve action potential recording to guide the choice of surgical procedure is often useful.
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              Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                14 December 2016
                December 2016
                : 17
                : 12
                : 2101
                Affiliations
                Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA; rsulliv1@ 123456health.usf.edu (R.S.); tdailey@ 123456health.usf.edu (T.D.); kduncan3@ 123456health.usf.edu (K.D.)
                Author notes
                [* ]Correspondence: nabel@ 123456health.usf.edu (N.A.); cborlong@ 123456health.usf.edu (C.V.B.); Tel.: +1-813-974-3988 (N.A. & C.V.B.)
                [†]

                These authors contributed equally to this work.

                Article
                ijms-17-02101
                10.3390/ijms17122101
                5187901
                27983642
                267b4f94-8c86-4dea-8087-2b0b9edf6bec
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 October 2016
                : 08 December 2016
                Categories
                Review

                Molecular biology
                regeneration,schwann cells,nerve graft,axonal injury,combination therapy,growth factors

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