Functional recovery after complete contusion injury to the spinal cord and transplantation of human neuroteratocarcinoma neurons in rats.
OBJECTIVE
Human neuroteratocarcinoma (hNT)-derived neurons are differentiated postmitotic neurons derived from a human teratocarcinoma cell line following treatment with retinoic acid. In preclinical transplantation studies investigators have demonstrated both their safety as a source of neurons for transplantation and efficacy in treating stroke-related behavioral deficits. The objective of this study was to examine whether hNT neurons transplanted in an area of complete spinal cord contusion would improve electrophysiological measures of spinal cord function.


METHODS
Complete spinal cord contusion injury, defined as the complete loss of motor evoked potentials (MEPs), was produced in 30 rats at T-8. Ten rats with contused spinal cords underwent transplantation with hNT neurons within the site of contusion immediately after injury (immediate transplant group). Ten rats underwent hNT neuron transplantation following a 2-week evaluation for loss of MEPs (delayed transplant group). Ten other rats with contusion injury served as a spinal cord injury control group, and 10 rats underwent only a T-8 laminectomy and served as non-injured controls. All rats survived 8 weeks after transplantation. In the delayed transplant group significant functional recovery was observed, as demonstrated by return of MEPs and a modest improvement of motor function. Immunohistochemical analysis showed the survival, integration, and long fiber outgrowth of the grafted hNT neurons.


CONCLUSIONS
These findings suggest that the transplantation of the hNT neurons may be an effective means of reestablishing electrical connectivity of the injured spinal cord.
Center for Aging and Brain Repair, Department of Anatomy, College of Medicine, University of South Florida, Tampa 33612, USA. ssaporta@hsc.usf.edu
Samuel
S
Saporta
A Shahram
AS
Makoui
Alison E
AE
Willing
Marcel
M
Daadi
David W
DW
Cahill
Paul R
PR
Sanberg
D000818:Animals; D003288:Contusions / Q000503:physiopathology* / Q000601:surgery*; D004594:Electrophysiology; D019054:Evoked Potentials, Motor; D006801:Humans; D008297:Male; D009474:Neurons / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000601:surgery; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D018243:Teratocarcinoma / Q000473:pathology*