Clinical feasibility for cell therapy using human neuronal cell line to treat neuropathic behavioral hypersensitivity following spinal cord injury in rats.
Management of neuropathic pain remains problematic; however, cell therapy to treat the effects of pain on the sensory system after spinal cord injury (SCI) could be a useful approach. Since many clinical trials ultimately do not succeed, use of cell therapy will require that safety and efficacy issues be addressed early in preclinical rat studies. We used the human neuronal cell line hNT2.17, which secretes the inhibitory neurotransmitters gamma-aminobutyric acid and glycine, in an excitotoxic SCI pain model after intraspinal injection of quisqualic acid into rats. One week after lumbar transplant of these cells, behavioral hypersensitivity was permanently reversed. Antinociceptive grafts displayed an optimal transplant time that included moderate effectiveness with chronic SCI and late graft placement and that required a minimal course of cyclosporine A 2 weeks after transplant for durable reversal of painlike behaviors. In addition, grafts did not need to be placed near the SCI level to be effective. These data suggest not only that these cells are safe and efficacious but also that they could be an effective clinical tool for treating SCI-associated neuropathic pain.
Eaton
Mary J
MJ
Department of Veterans Affairs Medical Center, Miami, FL 33125, USA. meatonscience@gmail.com
Wolfe
Stacey Q
SQ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009437:Neuralgia / Q000628:therapy*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D013116:Spinal Cord / Q000187:drug effects / Q000601:surgery; D013119:Spinal Cord Injuries / Q000150:complications*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D005680:gamma-Aminobutyric Acid; D016318:Quisqualic Acid; D005998:Glycine