We are initiating the creation and study of the use of two other human cell lines: (1) reversibly immortalized olfactory-ensheathing glia (OEG); and (2) reversibly immortalized human chromaffin cell lines. They will be used in studies of axonal regeneration and amelioration of pain, respectively, in rat models of those injuries. Both cell lines represent the creation of clinical tools for the treatment of the human problems.
The various cell and molecular strategies and the understanding and evaluation of the mechanisms of the induction and maintenance of chronic pain and spasticity after SCI will, I hope, provide the foundation for the development of the use of cell therapy and gene transfer after SCI in a clinical setting that could be established here at The Miami Project. My major scientific and philosophical aim is to move successful basic research to clinical applications for human medical problems as quickly as possible.
Eaton MJ (2003) Common animal models for spasticity and pain. J Rehab Res Dev 40:41-54. [Abstract]
Sagen J, Eaton MJ (2003) Cellular implantation for the treatment of chronic pain. In: Pain: Current understanding, emerging therapies, and novel approaches to drug discovery. SK Schmidt (ed). Chpt 67, pp.815-833.
Hains BC, Johnson KM, Eaton MJ, Willis WD, and CE Hulsebosch (2003) Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat. Neuroscience 116:1097 - 1110. [Abstract]
Hains BC, Yucra JA, Eaton MJ, Hulsebosch CE (2002) Intralesion transplantation of serotonergic precursors enhances locomotor recovery but has no effect on development of chronic central pain following hemisection injury in rats. Neurosci Lett 324:222-226. [Abstract]
Eaton MJ, B Blits, MJ Ruitenberg, J Verhaagen, and M Oudega (2002) Amelioration of chronic neuropathic pain by adeno-associated viral (AAV) vector-mediated overexpression of BDNF in the rat spinal cord. Gene Ther 9:1387-1395. [Abstract]
Eaton MJ, Herman JP, Jullien N, Lopez T, Martinez M, Huang J (2002) Immortalized chromaffin cells disimmortalized with Cre/lox site-directed recombination for use in cell therapy for pain. Exp Neurol 175:49-60. [Abstract]
Eaton M.J, Martinez MA, Karmally S, Lopez T, Sagen J (2001) Initial characterization of the transplant of immortalized chromaffin cells for the attenuation of chronic neuropathic pain. Cell Transplant. 9: 637-656. [Abstract]
Eaton MJ (2000) Emerging cell and molecular strategies for the study and treatment of painful peripheral neuropathies. J Periph Nerv Sys 5:59-74. [Abstract]
Eaton MJ, Plunkett JA, Martinez MA, Lopez T, Karmally S, Cejas P, Whittemore SR (1999) Transplants of neuronal cells bio_engineered to synthesize GABA alleviate chronic neuropathic pain. Cell Transplant 8:87-101. [Abstract]
Eaton MJ, Karmally S, Martinez MA, Plunkett JA, Lopez T, and Cejas P. (1999) Lumbar transplant of neurons genetically modified to secrete galanin reverse pain-like behaviors after partial sciatic nerve injury. J Periph Nerv Sys 4:245-257. [Abstract]
Eaton MJ, Santiago DI, Dancausse HA, Whitemore SR (1997) Lumbar transplants of serotonergic neurons alleviates chronic neuropathic pain. Pain 72:59-69. [Abstract]
We are rapidly continuing to implement basic and clinical studies utilizing cell lines for the treatment of the consequences of SCI. Ongoing research has been the development, with molecular biological techniques, neuronal & chromaffin rat cell lines that secrete a variety of agents. These agents include the neurotransmitters serotonin (5HT), GABA, galanin and catecholamines, as well as the neurotrophin BDNF, as well as the opioid peptide met-enkephalin. One major goal is to examine the potential of these cell lines to alleviate induced chronic neuropathic and neurogenic pain in rodent models of tonic, peripheral and central spinal injury by transplantation of these cells near the lumbar spinal cord pain centers. Since intractable pain after spinal cord injury in humans remains a major clinical problem, use of transplanted cells that function as biologic "minipumps" to secrete molecules such as neurotransmitters, neurotrophins, and peptides tests the hypothesis that transplants can alter the rate and outcome of recovery in CNS injury and chronic pain.