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      Stem cells for spinal cord regeneration: Current status

      review-article

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          Abstract

          Background:

          Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations/ variants thereof.

          Methods:

          In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required.

          Results:

          Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role.

          Conclusion:

          The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level.

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          Most cited references174

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          Glutamate neurotoxicity and diseases of the nervous system.

          D Choi (1988)
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            Hypoxia requires notch signaling to maintain the undifferentiated cell state.

            In addition to controlling a switch to glycolytic metabolism and induction of erythropoiesis and angiogenesis, hypoxia promotes the undifferentiated cell state in various stem and precursor cell populations. Here, we show that the latter process requires Notch signaling. Hypoxia blocks neuronal and myogenic differentiation in a Notch-dependent manner. Hypoxia activates Notch-responsive promoters and increases expression of Notch direct downstream genes. The Notch intracellular domain interacts with HIF-1alpha, a global regulator of oxygen homeostasis, and HIF-1alpha is recruited to Notch-responsive promoters upon Notch activation under hypoxic conditions. Taken together, these data provide molecular insights into how reduced oxygen levels control the cellular differentiation status and demonstrate a role for Notch in this process.
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              Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein.

              Adult mammalian axon regeneration is generally successful in the peripheral nervous system (PNS) but is dismally poor in the central nervous system (CNS). However, many classes of CNS axons can extend for long distances in peripheral nerve grafts. A comparison of myelin from the CNS and the PNS has revealed that CNS white matter is selectively inhibitory for axonal outgrowth. Several components of CNS white matter, NI35, NI250(Nogo) and MAG, that have inhibitory activity for axon extension have been described. The IN-1 antibody, which recognizes NI35 and NI250(Nogo), allows moderate degrees of axonal regeneration and functional recovery after spinal cord injury. Here we identify Nogo as a member of the Reticulon family, Reticulon 4-A. Nogo is expressed by oligodendrocytes but not by Schwann cells, and associates primarily with the endoplasmic reticulum. A 66-residue lumenal/extracellular domain inhibits axonal extension and collapses dorsal root ganglion growth cones. In contrast to Nogo, Reticulon 1 and 3 are not expressed by oligodendrocytes, and the 66-residue lumenal/extracellular domains from Reticulon 1, 2 and 3 do not inhibit axonal regeneration. These data provide a molecular basis to assess the contribution of Nogo to the failure of axonal regeneration in the adult CNS.
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                Author and article information

                Journal
                Surg Neurol Int
                SNI
                Surgical Neurology International
                Medknow Publications (India )
                2229-5097
                2152-7806
                2010
                25 December 2010
                : 1
                : 93
                Affiliations
                Department of Neurosurgery, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan
                Author notes
                *Corresponding author
                Article
                SNI-1-93
                10.4103/2152-7806.74240
                3019362
                21246060
                9b9a0c94-c446-458b-a023-75092b613a1f
                © 2010 Sobani ZA

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 September 2010
                : 01 November 2010
                Categories
                Review Article

                Surgery
                stem cells [a11.872],mesenchymal stem cells [a11.872.580],spinal cord injuries [c10.228.854.770]

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