Abstract
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 cells1, and transplanted skeletal myoblasts and keratinocytes can participate in the formation of normal tissue in host animals2–4. Cell transplantation in the central nervous system (CNS) has been proposed as a means of correcting neuronal dysfunction in diseases associated with neuronal loss5–7; 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 lesionsin 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 β-galactosidase gene gives rise to β-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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Spangude, G. J., Heimfeld, S. & Weissman, I. L. Science 241, 58–62 (1988).
Gussoni, E. et al. Nature 356, 435–438 (1992).
Dhawan, J. et al. Science 254, 1509–1512 (1991).
Morgan, J. R., Barrandon, Y., Green, H. & Mulligan, R. C. Science 237, 1476–1479 (1987).
Lindvall, D. et al. Science 247, 574–577 (1990).
Renfranz, P. J., Cunningham, M. J. & McKay, R. D. G. Cell 66, 713–729 (1991).
Snyder, E. Y. et al. Cell 68, 33–51 (1992).
Raff, M. C., Miller, R. H. & Noble, M. Nature 303, 390–396 (1983).
Blakemore, W. F. & Crang, A. J. Devl Neurosci. 10, 1–11 (1988).
Blakemore, W. F. & Crang, A. J. J. Neurocytol. 18, 519–528 (1989).
Crang, A. J. et al. J. Neuroimmun. 40, 243–254 (1992).
Bögler, O., Wren, D. R., Bamett, S. C., Land, H. & Noble, M. Proc. natn. Acad. Sci. U.S.A. 87, 6368–6372 (1990).
Raff, M. C. et al. Nature 274, 813–816 (1978).
Ranscht, B. Clapshaw, P. A., Price, J., Noble, M. & Siefert, W. Proc. natn. Acad Sci. U.S.A. 79, 2709–2713 (1982).
Price, J., Turner, D. & Cepko, C. L. Proc. natn. Acad. Sci. U.S.A. 84, 156–160 (1987).
Barres, B. A. et al. Cell 70, 31–46 (1992).
Mayer, M., Bögler, O. & Noble, M. (in the press).
Williams, B. P., Read, J. & Price, J. Neuron 7, 685–693 (1991).
Duncan, I. D. et al. J. Neurocytol. 17, 351–360 (1988).
Franklin, R. J. M., Crang, A. J. & Blakemore, W. F. J. Neurocytol. 20, 420–430 (1991).
Gransmuller, A., Clerin, E., Kruger, F., Gumpel, M. & Lachapelle, F. Glia 4, 580–589 (1991).
Gumpel, M., Baumann, N., Raoul, M. & Jacque, C. Neurosci. Lett. 37, 307–311 (1983).
Rosenbluth, J., Hasegawa, M., Shirasaki, N., Rosen, C. L. & Lui, Z. J. Neurocytol. 19, 718–730 (1990).
Gorman, C. F., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1054 (1982).
Feigner, P. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7417 (1987).
Franklin, R. J. M. & Barnett, S. C. Acta Neuropath. 81, 686–687 (1991).
Warrington, A. E., Barbarese, E. & Pfeiffer, S. E. J. Neurosci. Res. 34, 1–13 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Groves, A., Barnett, S., Franklin, R. et al. Repair of demyelinated lesions by transplantation of purified 0-2A progenitor cells. Nature 362, 453–455 (1993). https://doi.org/10.1038/362453a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/362453a0
This article is cited by
-
Cell replacement therapy with stem cells in multiple sclerosis, a systematic review
Human Cell (2023)
-
In vivo imaging reveals mature Oligodendrocyte division in adult Zebrafish
Cell Regeneration (2021)
-
Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss
Acta Neuropathologica Communications (2017)
-
Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury
Experimental & Molecular Medicine (2017)
-
Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders?
Molecular Neurobiology (2016)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.