Groves, A.K. et al. Repair of demyelinated lesions by transplantation of purified O-2A progenitors. Nature 362, 453-455

Department of Veterinary Medicine, University of Cambridge, Cambridge, England, United Kingdom
Nature (Impact Factor: 41.46). 05/1993; 362(6419):453-5. DOI: 10.1038/362453a0
Source: PubMed


The transplantation of well defined populations of precursor cells offers a means of repairing damaged tissue and of delivering therapeutic compounds to sites of injury or degeneration. For example, a functional immune system can be reconstituted by transplantation of purified haematopoietic stem cells, and transplanted skeletal myoblasts and keratinocytes can participate in the formation of normal tissue in host animals. Cell transplantation in the central nervous system (CNS) has been proposed as a means of correcting neuronal dysfunction in diseases associated with neuronal loss; it might also rectify glial cell dysfunction, with transplanted oligodendrocyte precursor cells eventually allowing repair of demyelinating damage in the CNS. Here we use co-operating growth factors to expand purified populations of oligodendrocyte type-2 astrocyte (O-2A) progenitor cells for several weeks in vitro. When injected into demyelinating lesions in spinal cords of adult rats, created in such a way as to preclude host-mediated remyelination, these expanded populations are capable of producing extensive remyelination. In addition, transplantation of O-2A progenitor cells genetically modified to express the bacterial beta-galactosidase gene gives rise to beta-galactosidase-positive oligodendrocytes which remyelinate demyelinated axons within the lesion. These results offer a viable strategy for the manipulation of neural precursor cells which is compatible with attempts to repair damaged CNS tissue by precursor transplantation.

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Available from: Sue C Barnett, Nov 20, 2015
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    • "Pre-existing mature oligodendrocytes are unlikely to contribute to remyelination, either directly or by de- and re-differentiating (similarly to Schwann cells in the peripheral nervous system [PNS] [45]), as previous studies have reported a lack of remyelination capacity of post-mitotic oligodendrocytes, even if they survive within a demyelinated lesion or are transplanted from a normally myelinating area into a lesion site [46, 47]. Conversely, rat OPCs transplanted into demyelinated areas can differentiate into myelinating oligodendrocytes and produce robust myelin [48]. Furthermore, dividing endogenous progenitor cells in the adult rat brain have been shown to respond to demyelination by differentiating into myelin-forming oligodendrocytes [49]. "
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    • "Early cell-culture studies showed that OPCs purified from rat optic nerves differentiate not only into oligodendrocytes but also into process-bearing “type-2 astrocytes” in the presence of serum factors, which led to the concept of bipotential oligodendrocyte type-2-astrocyte (O-2A) progenitor cells [38]. There are now controversial observations suggesting that bipotentiality of polydendrocytes might be real or an in vitro artifact [126, 128, 129], and most likely these cells are inherently capable of differentiating into astrocytes but are prevented from fulfilling their astroglial fate in the normal in vivo environment [118]. "
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    • "Glial cell death via apoptosis, particularly loss of myelinating OLGs, may result in consequent axonal demyelination (Jensen et al. 1999; Tamura et al. 2005; Warden et al. 2001). In support this hypothesis, remyelination of the spinal cord axons via cell transplantation (Akiyama et al. 2002; Groves et al. 1993; Keirstead et al. 2005) or transplants combined with cAMP elevation or neurotrophic factors (Cao et al. 2005; Pearse et al. 2004) have been shown to improve functional recovery in SCI rodents significantly. In addition, RhoA might negatively regulate myelin formation in the CNS because RhoA activation by Lingo1, a protein present in OLGs, appears to suppress myelination of CNS axons (Mi et al. 2005; Mi et al. 2009). "
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