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      Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities

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          Abstract

          Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.

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          Fibroblast precursors in normal and irradiated mouse hematopoietic organs.

          A. Friedenstein, J Gorskaja, N N Kulagina (1976)
          Using the in vitro colony assay, clonogenic fibroblast precursor cells (CFU-F) were detected in the bone marrow, spleen and thymus from adult mice. The survival curve for CFU-F of mouse bone marrow irradiated in vitro has a D0 of 220 r. Regeneration of bone marrow CFU-F after whole-body irradiation with 150 r is characterized by a marked secondary loss and post-irradiation lag and dip, lasting 6 days, followed by return to normal values by about the 25th day. This pattern of post-radiation recovery of CFU-F is similar to that of the CFU-s. In addition, during the first 6 hours following irradiation the number of CFU-F increased approximately twofold.
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            Adult bone marrow stromal cells differentiate into neural cells in vitro.

            J. Sanchez-Ramos, S. Song, F Cardozo-Pelaez … (2000)
            Bone marrow stromal cells (BMSC) normally give rise to bone, cartilage, and mesenchymal cells. Recently, bone marrow cells have been shown to have the capacity to differentiate into myocytes, hepatocytes, and glial cells. We now demonstrate that human and mouse BMSC can be induced to differentiate into neural cells under experimental cell culture conditions. BMSC cultured in the presence of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural precursors. These cultures also expressed glial fibrillary acidic protein (GFAP) and neuron-specific nuclear protein (NeuN). When labeled human or mouse BMSC were cultured with rat fetal mesencephalic or striatal cells, a small proportion of BMSC-derived cells differentiated into neuron-like cells expressing NeuN and glial cells expressing GFAP. Copyright 2000 Academic Press.
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              Identification of a novel population of muscle stem cells in mice

              Zhuqing Qu-Petersen, Bridget Deasy, Ron Jankowski … (2002)
              Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell–mediated therapies.
              Article 0 comments Cited 145 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Katalin Prokai-Tatrai: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 05 January 2017
                Publication date Collection: January 2017
                Volume: 18
                Issue: 1
                Electronic Location Identifier: 94
                Affiliations
                [1 ]Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; john94007@ 123456163.com
                [2 ]Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; SAJones@ 123456som.umaryland.edu
                [3 ]Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
                [4 ]Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
                [5 ]Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
                [6 ]Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
                Author notes
                [* ]Correspondence: xjia@ 123456som.umaryland.edu ; Tel.: +1-410-706-5026
                Article
                Publisher ID: ijms-18-00094
                DOI: 10.3390/ijms18010094
                PMC ID: 5297728
                PubMed ID: 28067783
                SO-VID: 85ffb25b-15af-4552-af9c-d80bcacc987f
                Copyright © © 2017 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                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
                Date received : 15 December 2016
                Date accepted : 27 December 2016
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: peripheral nerve,regeneration,stem cells,transplantation
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: peripheral nerve, regeneration, stem cells, transplantation

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