Transplantation Strategies in Spinal Cord Regeneration

  • Howard Nornes
  • Anders Björklund
  • Ulf Stenevi


Transplantation models in the brain have proven successful under conditions in which transplants serve as a “bridge” for the regeneration of axons across a site of injury, or as “release” or “driving” units to replace missing inputs to a particular target area.1–8 Similar models have been applied to the mammalian spinal cord including: (1) intraspinal transplants to form a bridge for the regeneration of spinal cord axons, (2) extraspinal transplants with only the end or ends of the transplants inserted into the cord to bypass the region of injury, and (3) intraspinal neural implants to replace missing supraspinal inputs. These models demonstrate that neurons of the spinal cord possess the ability to regenerate axons several millimeters into both intrinsic and extrinsic transplants; however, the growth of these axons into the tissue of the host spinal cord has been limited. By contrast, embryonic CNS neurons transplanted into the adult spinal cord, possess the ability to grow axons that penetrate several millimeters into spinal cord tissue. This review provides an overview of the attempts to promote regeneration of spinal cord connections by using various transplantation paradigms.


Spinal Cord Sciatic Nerve Spinal Cord Tissue Spinal Cord Transection Spinal Cord Regeneration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Björklund, A., and Stenevi, U., 1979, Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants, Brain Res. 17:555.CrossRefGoogle Scholar
  2. 2.
    Björklund, A., Stenevi, U., Dunnett, S. B., and Iversen, S. D., 1981, Functional reactivation of the deafferented neostriatum by nigral transplants, Nature (London) 289:497.CrossRefGoogle Scholar
  3. 3.
    Perlow, M. J., Freed, W. J., Hoffer, B. J., Seiger, Å., Olson, L., and Wyatt, R. J., 1979, Brain grafts reduce motor abnormalities produced by destruction of neostriatal dopamine system, Science 204:643.PubMedCrossRefGoogle Scholar
  4. 4.
    Freed, W. J., Perlow, M. J., Karoum, F., Seiger, Å., Olson, L., Hoffer, B. J., and Wyatt, R. J., 1980, Restoration of dopaminergic functions by grafting of fetal rat substantia nigra to the caudate nucleus: Long-term behavioral, biochemical, and histochemical studies, Ann. Neurol. 8:510.PubMedCrossRefGoogle Scholar
  5. 5.
    Gash, D., Sladek, J. R., Jr., and Sladek, S. D., 1980, Functional development of grafted vasopressin neuron, Science 210:1367.PubMedCrossRefGoogle Scholar
  6. 6.
    Kromer, L. F., Björklund, A., and Stenevi, U., 1980, Regeneration of the septohippocampal pathways in adult rats is promoted by utilizing embryonic hippocampal implants as bridges, Brain Res. 210:173.CrossRefGoogle Scholar
  7. 7.
    Dunnett, S. B., Low, W. C., Iversen, S. D., Stenevi, U., and Björklund, A., 1982, Septal transplants restore maze learning in rats with fornix-fimbria lesion, Brain Res. 251:335.PubMedCrossRefGoogle Scholar
  8. 8.
    Krieger, D. T., Perlow, M. J., Gibson, M. J., Davies, T. F., Zimmerman, E. A., Ferin, M., and Charlton, H. M., 1982, Brain graft reverse hypogonadism of gonadotropin releasing hormone deficiency, Nature (London) 298:468.CrossRefGoogle Scholar
  9. 9.
    Tello, F., 1911, La influencia del neurotropismo en la regeneracio de los centros nervioses, Trab., Lab. Invest. Biol. Madred 9:123.Google Scholar
  10. 10.
    Ramón y Cajal, S., 1928, Degeneration and regeneration of the nervous system (R. M. May, ed., transl.), Hafner, New York.Google Scholar
  11. 11.
    Puchala, E., and Windle, W. F., 1977, The possibility of structural and functional restoration after spinal cord injury: A review, Exp. Neurol. 55:1.PubMedCrossRefGoogle Scholar
  12. 12.
    Guth, L., Brewer, C. R., Collins, W. F., Goldberger, M. E., and Perl, E. R., 1980, Criteria for evaluating spinal cord regeneration experiment, Exp. Neurol. 69:1.PubMedCrossRefGoogle Scholar
  13. 13.
    Sugar, O., and Gerard, R. W., 1940, Spinal cord regeneration in the rat, J. Neurophysiol. 3:1Google Scholar
  14. 14.
    Barnard, J. W., and Carpenter, W., 1950, Lack of regeneration in spinal cord of rat, J. Neurophysiol. 13:223.PubMedGoogle Scholar
  15. 15.
    Feigin, I., Geller, E. H., and Wolf, A., 1951, Absence of regeneration in the spinal cord of the young rat, J. Neuropathol. Exp. Neurol. 10:42-.CrossRefGoogle Scholar
  16. 16.
    Brown, J. O., and McCouch, G. P., 1947, Abortive regeneration of the transected spinal cord, J. Comp. Neurol. 87:131.PubMedCrossRefGoogle Scholar
  17. 17.
    Kao, C. C., Shimizu, Y., Perkins, L. C., and Freeman, L. W., 1970, Experimental use of cultured cerebellar cortical tissue to inhibit the collagenous scar following spinal cord transection, J. Neurosurg. 3:127.Google Scholar
  18. 18.
    Kao, C. C., 1974, Comparison of wound healing process in transected spinal cords grafted with autologous brain tissue, sciatic nerve, and nodose ganglia, Exp. Neurol. 44:424.PubMedCrossRefGoogle Scholar
  19. 19.
    Kao, C. C., Chang, L. W., and Bloodworth, J. M. B., Jr., 1977, Successful axonal regeneration to bridge the gap of transected mammalian spinal cords: An electron microscopic study of the results of delayed microsurgical nerve grafting, Exp. Neurol. 54:591–615.PubMedCrossRefGoogle Scholar
  20. 20.
    Kao, C. C., Chang, L. W., and Bloodworth, J. M. B., Jr., 1977, The mechanism of spinal cord cavitation following spinal cord transection. Part 3. Delayed grafting with and without retransection, J. Neurosurg. 46:757.PubMedCrossRefGoogle Scholar
  21. 21.
    Richardson, P. M., McGuiness, U. M., and Aguayo, A. J., 1980, Axons from CNS neurons regenerate into PNS grafts, Nature (London) 284:264.CrossRefGoogle Scholar
  22. 22.
    Richardson, P. M., McGuiness, U. M., and Aguayo, A. J., 1982, Peripheral nerve autografts to the rat spinal cord: Studies with axonal tracing methods, Brain Res. 237:147.PubMedCrossRefGoogle Scholar
  23. 23.
    Blakemore, W. F., 1977, Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve, Nature (London) 266:68.CrossRefGoogle Scholar
  24. 24.
    Duncan, I. D., Aguayo, A. J., Bunge, R. P., and Wood, P. M., 1981, Transplantation of rat Schwann cells grown in tissue culture into mouse spinal cord. J. Neurol. Sci. 49:241.PubMedCrossRefGoogle Scholar
  25. 25.
    Wrathal, J. R., Rigamonte, D. D., Braford, M. R., and Kao, C. C., 1982, Reconstruction of the contused cap spinal cord by the delayed nerve graft technique and cultured peripheral nonneuronal cells, Acta Neuropathol. 57:59.CrossRefGoogle Scholar
  26. 26.
    Björklund, A., Katzman, R., Stenevi, U., and West, K. A., 1971, Development and growth of axonal sprouts from noradrenaline and 5-hydroxytryptamine neurons in the rat spinal cord, Brain Res. 31:21.PubMedCrossRefGoogle Scholar
  27. 27.
    Aihara, H., 1970, Autotransplantation of cultured cerebellar cortex for spinal cord reconstruction, Brain Nerve 22:769 (in Japanese).PubMedGoogle Scholar
  28. 28.
    Bregman, B. S., and Reier, P. J., 1982, Transplantation of fetal spinal cord tissue to injured spinal cord in neonatal and adult rats, Soc. Neurosci. Abstr. 8:870.Google Scholar
  29. 29.
    Nornes, H., Björklund, A., and Stenevi, U., 1983, Reinnervation of the denervated adult spinal cord of rats by intraspinal transplants of embryonic brainstem neurons, Cell Tissue Res. 230:15.PubMedCrossRefGoogle Scholar
  30. 30.
    Nornes, H., Björklund, A., and Stenevi, U., 1981, Embryonic CNS tissue implanted into adult spinal cords, Soc. Neurosci. Abstr. 7:678.Google Scholar
  31. 31.
    Campbell, J. B., Andrew, C., Bassett, L., Husby, J., and Noback, C. R., 1958, Axonal regeneration in the transected adult feline spinal cord. Surg. Forum 8:528.Google Scholar
  32. 32.
    Bassett, C. A. L., Campbell, J. B., and Husby, J., 1959, Peripheral nerve and spinal cord regenerative factors leading to success of a tubulation technique employing Millipore, Exp. Neurol. 1:386.PubMedCrossRefGoogle Scholar
  33. 33.
    de la Torre, J. C., 1982, Catecholamine fibre regeneration across a collagen bioimplant after spinal cord transection, Brain Res. Bull. 9:545.PubMedCrossRefGoogle Scholar
  34. 34.
    Turbes, C. C., and Freeman, L. W., 1958, Peripheral nerve-spinal cord anastomosis for experimental cord transection, Neurology 8:857.PubMedGoogle Scholar
  35. 35.
    Perkins, L., Babbini, A., and Freeman, L. W., 1964, Distal-proximal nerve implants in spinal cord transection, Neurology 14:949.PubMedGoogle Scholar
  36. 36.
    Galabov, G., 1966, Regeneration of sectioned spinal cord by implantation of a peripheral nerve, Comp. Neurol. Acad. Bulg. Sci. 19:449.Google Scholar
  37. 37.
    David, S., and Aguayo, A. J., 1981, Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats, Science 214:931.PubMedCrossRefGoogle Scholar
  38. 38.
    Andén, N.-E., Jukes, M. G. M., and Lundberg, A., 1966, The effect of DOPA on the spinal cord. 2. A pharmacological analysis, Acta Physiol. Scand. 67:387.PubMedCrossRefGoogle Scholar
  39. 39.
    Jankowska, E., Jukes, M. G. M., and Lundberg, A., 1967, The effect of DOPA on the spinal cord. 6. Half-centre organization of interneurons transmitting effects from flexor reflex afferents, Acta Physiol. Scand. 70:389.PubMedCrossRefGoogle Scholar
  40. 40.
    Grillner, S., 1973, Locomotion in the spinal cat, in: Control of Posture and Locomotion (R. B. Stein, K. G. Pearson, R. S. Smith, and J. B. Redford, eds), pp. 515–536, Plenum Press, New York.Google Scholar
  41. 41.
    Lundberg, A., 1982, Inhibitory control from brain stem of transmission from primary afferents to motorneurons, primary afferent terminals and ascending pathways, in: Brain Stem Control of Spinal Mechanisms (B. Sjölund and A. Björklund, eds.), Elsevier Biomedical Press, Amsterdam, New York, Oxford.Google Scholar
  42. 42.
    Nygren, L. G., Olson, L., and Seiger, Å., 1977, Monoaminergic reinnervation of transected spinal cord by homologous fetal brain grafts, Brain Res. 129:227.PubMedCrossRefGoogle Scholar
  43. 43.
    Segal, M., Stenevi, U., and Björklund, A., 1981, Reformation in adult rats of functional septo-hippocampal connection by septal neurons regenerating across an embryonic hippocampal connection by septal neurons regenerating across an embryonic hippocampal bridge, Neurosci. Lett. 27:7.PubMedCrossRefGoogle Scholar
  44. 44.
    Stensaas, L. J., Burgess, P. R., and Horch, K. W., 1979, Regenerating dorsal root axons blocked by spinal cord astrocytes, Soc. Neurosci. Abstr. 5:684.Google Scholar
  45. 45.
    Nathaniel, E. J. H., and Nathaniel, D. R., 1973, Regeneration of dorsal root fibers into the adult rat spinal cord, Exp. Neurol. 40:333.PubMedCrossRefGoogle Scholar
  46. 46.
    Perkins, C. S., Carlstedt, T., Mizuno, K., and Aguayo, A. J., 1980, Failure of regenerating dorsal root axons to regrow into the spinal cord. Can. J. Neurol. Sci. 7:323.Google Scholar
  47. 47.
    Rovainen, C. M., 1976, Regeneration of Müller and Mauthner axon after spinal transection in the larval lamprey, J. Comp. Neurol. 168:545.PubMedCrossRefGoogle Scholar
  48. 48.
    Selzer, M. E., 1978, Mechanism of functional recovery and regeneration after spinal cord transection in larval sea lamprey, J. Physiol. (London) 277:395.Google Scholar
  49. 49.
    Shik, M. L., Severin, F. V., and Orlovsky, G. N., 1966, Control of walking and running by means of electrical stimulation of the midbrain, Biophysics 11:756.Google Scholar
  50. 50.
    Stein, P. C., 1978, Motor systems with specific reference to control of locomotion, Annu. Rev. Neurosci. 1:61.PubMedCrossRefGoogle Scholar
  51. 51.
    Björklund, A., Segal, M., and Stenevi, U., 1979, Functional reinnervation of rat hippocampus by locus coeruleus implants, Brain Res. 170:409.PubMedCrossRefGoogle Scholar
  52. 52.
    Low, W. C., Lewis, P. R., Bunch, S. B., Dunnett, S. B., Thomas, S. R., Iversen, S. D., Björklund, A., and Stenevi, U., 1982, Functional recovery following neural transplants of embryonic septal nuclei into adult rats with septohippocampal lesions: The recovery of function, Nature (London) 300:260.CrossRefGoogle Scholar
  53. 53.
    Budakova, N. N., 1973, Stepping movements in the spinal cat due to DOPA administration, Fiz. Zh. SSSR im. I.M. Sechenova 59:1190.Google Scholar
  54. 54.
    Forssberg, H., and Grillner, S., 1973, The locomotion of the acute spinal cat injected with clonidine i. v., Brain Res. 50:184.PubMedCrossRefGoogle Scholar
  55. 55.
    Viala, D., and Buser, P., 1969, The efTects of DOPA and 5-HTP on rhythmic efferent discharges in hindlimb nerves in the rabbit, Brain Res. 12:437.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Howard Nornes
    • 1
  • Anders Björklund
    • 2
  • Ulf Stenevi
    • 2
  1. 1.Department of AnatomyColorado State UniversityFort CollinsUSA
  2. 2.Departments of Histology and OphthalmologyUniversity of LundLundSweden

Personalised recommendations