The Use of Transplanted Glial Cells to Reconstruct Glial Environments in the CNS

Department of Clinical Veterinary Medicine and MRC Cambridge Centre for Brain Repair, UK.
Brain Pathology (Impact Factor: 3.84). 11/1995; 5(4):443-50. DOI: 10.1111/j.1750-3639.1995.tb00623.x
Source: PubMed


Transplantation studies have demonstrated that glia-depleted areas of the CNS can be reconstituted by the introduction of cultured cells. Thus, the influx of Schwann cells into glia-free areas of demyelination in the spinal cord can be prevented by the combined introduction of astrocytes and cells of the O-2A lineage. Although Schwann cell invasion of areas of demyelination is associated with destruction of astrocytes, the transplantation of rat tissue culture astrocytes ("type-1") alone cannot suppress this invasion, indicating a role for cells of the O-2A lineage in reconstruction of glial environments. By transplanting different glial cell preparations and manipulating lesions so as to prevent meningeal cell and Schwann cell proliferation it is possible to demonstrate that the behaviour of tissue culture astrocytes ("type-1") and astrocytes derived from O-2A progenitor cells ("type-2") is different. In the presence of meningeal cells, tissue culture astrocytes clump together to form cords of cells. In contrast, type-2 astrocytes spread throughout glia-free areas in a manner unaffected by the presence of meningeal cells or Schwann cells. Thus, progenitor-derived astrocytes show a greater ability to fill glia-free areas than tissue culture astrocytes. Similarly, when introduced into infarcted white matter in the spinal cord, progenitor-derived astrocytes fill the malacic area more effectively than tissue culture astrocytes, although axons do not regenerate into the reconstituted area.

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    • "Transplanted Schwann cells myelinate CNS axons in vivo in a variety of experimental models, and can restore function to demyelinated axons. Similarly, in some myelin mutants, and following injection of toxins that kill astrocytes and oligodendrocytes, endogenous Schwann cells provide significant areas with long lasting and functional myelin (Blakemore, 1977; Duncan et al., 1981; Itoyama et al., 1983; Baron van Evercooren et al., 1992; Felts and Smith, 1992; Blakemore et al., 1995; Honmou et al., 1996; Duncan and Hoffman, 1997; Iwashita et al., 2000). With respect to the possibility of using Schwann cells as a therapeutic tool in MS, these observations indicate that cells of the Schwann cell lineage can in principle, and given the right conditions, achieve stable and functional myelin repair within the CNS. "
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    ABSTRACT: Cell transplant therapies are currently under active consideration for a number of degenerative diseases. In the immune-mediated demyelinating-neurodegenerative disease multiple sclerosis (MS), only the myelin sheaths of the CNS are lost, while Schwann cell myelin of the PNS remains normal. This, and the finding that Schwann cells can myelinate CNS axons, has focussed interest on Schwann cell transplants to repair myelin in MS. However, the experimental use of these cells for myelin repair in animal models has revealed a number of problems relating to the incompatibility between peripheral glial cells and the CNS glial environment. Here, we have tested whether these difficulties can be avoided by using an earlier stage of the Schwann cell lineage, the Schwann cell precursor (SCP). For direct comparison of these two cell types, we implanted Schwann cells from post-natal rat nerves and SCPs from embryo day 14 (E14) rat nerves into the CNS under various experimental conditions. Examination 1 and 2 months later showed that in the presence of naked CNS axons, both types of cell form myelin that antigenically and ultrastructurally resembles that formed by Schwann cells in peripheral nerves. In terms of every other parameter we studied, however, the cells in these two implants behaved remarkably differently. As expected from previous work, Schwann cell implants survive poorly unless the cells find axons to myelinate, the cells do not migrate significantly from the implantation site, fail to integrate with host oligodendrocytes and astrocytes, and form little myelin when challenged with astrocyte-rich environment in the retina. Following SCP implantation, on the other hand, the cells survive well, migrate through normal CNS tissue, interface smoothly and intimately with host glial cells and myelinate extensively among the astrocytes of the retina. Furthermore, when implanted at a distance from a demyelinated lesion, SCPs but not Schwann cells migrate through normal CNS tissue to reach the lesion and generate new myelin. These features of SCP implants are all likely to be helpful attributes for a myelin repair cell. Since these cells also form Schwann cell myelin that is arguably likely to be resistant to MS pathology, they share some of the main advantages of Schwann cells without suffering from the disadvantages that render Schwann cells less than ideal candidates for transplantation into MS lesions.
    Brain 09/2007; 130(Pt 8):2175-85. DOI:10.1093/brain/awm125 · 9.20 Impact Factor
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    ABSTRACT: [EN]Development. Brain and spinal cord lesions have an increasing social and economic importance. Accidental trauma of various kinds is the main cause of mortality of children and young adults in developed countries. Only cardiac disease and cancer surpass the number of death caused by accidents and, examining the number of potential work-years lost, CNS lesions surpass all other problems. Most brain and spinal cord injuries cause chronic incapacity and frequently occur to individuals under 45 years of age. Edema and other acute events can be efficiently treated and CNS lesions may not be mortal, but are incurable. Conclusion. The final outcome of CNS injury depend on the area damaged and the extent of the lesion, but the best present therapies can offer is relief of the symptoms and rehabilitation. This review examines the present state of functional repair of experimental central nervous system trauma. [ES]Desarrollo. Las lesiones de cerebro y médula espinal están adquiriendo una creciente importancia social y económica. En los países desarrollados, el trauma accidental es la causa principal de la muerte de niños y adultos jóvenes. Solamente las enfermedades cardíacas y el cáncer superan a los accidentes como causa de mortalidad y, si examinamos los años de trabajo potencial perdidos, las lesiones del sistema nervioso central (SNC) superan a todos los demás problemas. La mayoría de las lesiones de cerebro y médula espinal ocurren en individuos menores de 45 años de edad y causan incapacidad crónica. El edema y otros fenómenos de fase aguda pueden tratarse eficazmente y las lesiones del SNC no son mortales, pero sí incurables. Conclusión. Las consecuencias finales de una lesión del SNC dependen del lugar dañado y la magnitud de la lesión; lo mejor que las terapias actuales pueden ofrecer es alivio de los síntomas y rehabilitación. Esta revisión examina el estado actual de la reparación funcional de lesiones experimentales traumáticas del sistema nervioso central. El trabajo de nuestro equipo ha sido financiado por el CSIC, el FIS, la CICYT y la Unión Europea. Peer reviewed
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    Radioactivity in the Environment 01/2005; 7. DOI:10.1016/S1569-4860(04)07035-4
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