Optimizing the transplant dose of a human neuronal cell line graft to treat SCI pain in the rat

Abstract

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: 10 6, 10 5 and 10 3 cells. Behavioral hypersensitivity testing was performed weekly for 6 weeks following transplant. The dose of 10 6 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.