TY - JOUR
T1 - Optimizing the transplant dose of a human neuronal cell line graft to treat SCI pain in the rat
AU - Wolfe, Stacey Quintero
AU - Garg, Megha
AU - Cumberbatch, Nadia M.A.
AU - Furst, Cassandra
AU - Martinez, Miguel
AU - Hernandez, Massiel
AU - Reimers, Regine
AU - Berrocal, Yerko
AU - Gómez-Marín, Orlando
AU - Eaton, Mary J.
N1 - Funding Information:
This study was supported by the Department of Veteran's Affairs: Office of Research and Development, Rehabilitation R&D Merit Review and the VA RR&D Center of Excellence in Functional Recovery in Chronic Spinal Cord Injury, Miami, FL; the American Syringomyelia Alliance Project; the Column of Hope, Chiari and Syringomyelia Research Foundation; the Miami Project to Cure Paralysis, Miller School of Medicine, Miami, FL.
PY - 2007/3/6
Y1 - 2007/3/6
N2 - Neuropathic pain is a prevalent and difficult problem in the setting of spinal cord injury (SCI). The use of cellular transplant therapy to treat this pain has been successful with the use of a human neuronal cell line, hNT2.17 [M.J. Eaton, S.Q. Wolfe, M.A. Martinez, M. Hernandez, C. Furst, J. Huang, B.R. Frydel, O. Gomez-Marin, Subarachnoid transplant of a human neuronal cell line attenuates chronic allodynia and hyperalgesia after excitotoxic SCI in the rat, J. Pain 8 (2007) 33-50]. Intrathecal transplant of these cells potently reverses behavioral hypersensitivity after excitotoxic spinal cord injury in the rat model. This study focuses on delineating the optimal dose of these cell grafts in the same model. Two weeks after intraspinal injection of quisqualic acid (QUIS) with subsequent behavioral hypersensitivity, terminally differentiated hNT2.17 cells were transplanted into 300 g Wistar-Furth rats in a logarithmic variation of doses: 106, 105 and 103 cells. Behavioral hypersensitivity testing was performed weekly for 6 weeks following transplant. The dose of 106 cells (or approximately 3 million/kg) potently and permanently reversed both cutaneous allodynia (CA) and thermal hyperalgesia (TH). Reduced transplant doses of the hNT2.17 cell line did not permanently reverse behavioral hypersensitivity, suggesting that there is an optimal dose that can be used as a clinical tool to treat SCI-associated neuropathic pain.
AB - Neuropathic pain is a prevalent and difficult problem in the setting of spinal cord injury (SCI). The use of cellular transplant therapy to treat this pain has been successful with the use of a human neuronal cell line, hNT2.17 [M.J. Eaton, S.Q. Wolfe, M.A. Martinez, M. Hernandez, C. Furst, J. Huang, B.R. Frydel, O. Gomez-Marin, Subarachnoid transplant of a human neuronal cell line attenuates chronic allodynia and hyperalgesia after excitotoxic SCI in the rat, J. Pain 8 (2007) 33-50]. Intrathecal transplant of these cells potently reverses behavioral hypersensitivity after excitotoxic spinal cord injury in the rat model. This study focuses on delineating the optimal dose of these cell grafts in the same model. Two weeks after intraspinal injection of quisqualic acid (QUIS) with subsequent behavioral hypersensitivity, terminally differentiated hNT2.17 cells were transplanted into 300 g Wistar-Furth rats in a logarithmic variation of doses: 106, 105 and 103 cells. Behavioral hypersensitivity testing was performed weekly for 6 weeks following transplant. The dose of 106 cells (or approximately 3 million/kg) potently and permanently reversed both cutaneous allodynia (CA) and thermal hyperalgesia (TH). Reduced transplant doses of the hNT2.17 cell line did not permanently reverse behavioral hypersensitivity, suggesting that there is an optimal dose that can be used as a clinical tool to treat SCI-associated neuropathic pain.
KW - Cellular transplant
KW - hNT2.17
KW - Intrathecal dose
KW - Neuronal cell line
KW - Neuropathic pain
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=33847016417&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847016417&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2006.10.067
DO - 10.1016/j.neulet.2006.10.067
M3 - Article
C2 - 17306458
AN - SCOPUS:33847016417
VL - 414
SP - 121
EP - 125
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -