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Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord

Nature Medicine volume 5, pages 1410–1412 (1999)Cite this article

Abstract

Transplantation approaches using cellular bridges1,2, fetal central nervous system cells3,4,5, fibroblasts expressing neurotrophin-3 (ref. 6), hybridoma cells expressing inhibitory protein-blocking antibodies7, or olfactory nerves ensheathing glial cells8 transplanted into the acutely injured spinal cord have produced axonal regrowth or functional benefits. Transplants of rat or cat fetal spinal cord tissue into the chronically injured cord survive and integrate with the host cord, and may be associated with some functional improvements9. In addition, rats transplanted with fetal spinal cord cells have shown improvements in some gait parameters10, and the delayed transplantation of fetal raphe cells can enhance reflexes11. We transplanted neural differentiated mouse embryonic stem cells into a rat spinal cord 9 days after traumatic injury. Histological analysis 2–5 weeks later showed that transplant-derived cells survived and differentiated into astrocytes, oligodendrocytes and neurons, and migrated as far as 8 mm away from the lesion edge. Furthermore, gait analysis demonstrated that transplanted rats showed hindlimb weight support and partial hindlimb coordination not found in 'sham-operated' controls or control rats transplanted with adult mouse neocortical cells.

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Figure 1: BrdU labeled ES cell-derived cells 2 weeks after transplantation.
Figure 2: Transplanted ES cell-derived cells differentiate into oligodendrocytes, astrocytes and neurons.
Figure 3: ES cell-derived cell transplantation improved behavioral recovery.

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Acknowledgements

This work was supported by National Institutes of Health grants NS01931, NS37927 (J.W.M.), NS32636 (D.W.C.) and RR-12309 (D.I.G.); the Alan A. and Edith L. Wolff Charitable Trust (D.I.G.); the Christopher Reeve Paralysis Foundation (J.W.M. and D.W.C.); and the Keck Foundation (J.W.M., D.W.C. and D.I.G.).

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Authors and Affiliations

  1. the Restorative Treatment and Research Center and Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, Box 8111, 660 S. Euclid Ave., St. Louis, 63110, Missouri, USA

    John W. McDonald, Xiao-Zhong Liu, Yun Qu, Su Liu, Shannon K. Mickey, David I. Gottlieb & Dennis W. Choi

  2. Department of Anatomy and Neurobiology, Washington University School of Medicine,

    David I. Gottlieb

  3. Box 8111, 660 S. Euclid Ave., St. Louis, 63110, Missouri, USA

    David I. Gottlieb

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  1. John W. McDonald
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  2. Xiao-Zhong Liu
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  4. Su Liu
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Correspondence to John W. McDonald.

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McDonald, J., Liu, XZ., Qu, Y. et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5, 1410–1412 (1999). https://doi.org/10.1038/70986

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