Alan Tessler received his M.D. degree from New York University and his postgraduate training in neurosurgery and neurology at the Hospital of the University of Pennsylvania. Since finishing training, Dr. Tessler has been a staff neurologist at Philadelphia's Department of Veterans Affairs Medical Center and carries out his research there and in the Department of Neurobiology and Anatomy at the Drexel University College of Medicine, where he is now Professor.
Neural transplants to enhance both neuron survival and regeneration
The goal of my research has been to understand the mechanisms that contribute to recovery after spinal cord injury and to use this knowledge to develop rational clinical treatments. Since recovery is likely to be enhanced both by rescuing damaged neurons that otherwise would have died and by enhancing regeneration of injured axons that otherwise would not have grown in the CNS, we study and seek to enhance both neuron survival and regeneration.
Our emphasis now is to use as transplants various types of cells that have been genetically modified to express neurotrophic factors, including fibroblasts, bone marrow stem cells and neural stem cells. We have found that fibroblasts and neural stem cells that have been engineered to express NT-3 rescue Clarke's nucleus neurons as efficiently as transplants of fetal spinal cord. We have also reported that fibroblasts that express BDNF rescue axotomized red nucleus neurons and in addition promote regeneration of rubrospinal axons and recovery of forelimb and hindlimb locomotor function.
We intend to continue similar experiments in which we assay the effects of transplants with quantitative anatomical tracing techniques and quantitative assays of behavior. The effects of spinal cord stem cells will be particularly interesting because such cells may be extremely supportive of axon regeneration. We have begun to apply these techniques to chronic injury models, and we plan to continue these studies.
"Critical interval for rescue of axotomized neurons by transplants"
Shibayama M, Matsui N, Himes BT, Murray M, and Tessler A
NeuroReport. 9 (1): 1-4, 1998.
"A DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats"
Takahashi K, Schwarz E, Ljubetic C, Murray M, Tessler A, and Saavedra RA
J. Comp. Neurol. 404: 159-171, 1999.
"Neurotrophic agents in fibrin glue mediate adult dorsal root regeneration into spinal cord"
Iwaya K, Mizoi K, Tessler A, and Itoh Y
Neurosurgery 44: 589-596, 1999.
"Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons"
Liu Y, Kim D, Himes BT, Chow SY, Jin H, Murray M, Tessler A, and Fischer I
J. Neurosci. 19 (11): 4370-4387, 1999.
"Red nucleus neurons of Bcl-2 over-expressing mice are protected from cell death induced by axotomy"
Zhou L, Connors T, Chen DF, Murray M, Tessler A, Kambin P, and Saavedra RA
NeuroReport 10: 3417-3421, 1999.
"Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons"
Jin Y, Tessler A, Fischer I, and Houle JD
Neurorehab. Neural Repair 14: 319-330, 2000.
"Characterization and intraspinal grafting of EGF/bFGF dependent neurospheres derived from embryonic rat spinal cord"
Chow, SY, Moul J, Tobias CA, Himes BT, Liu Y, Obrocka M, Hodge L, Tessler A, and Fischer I
Brain Res. 874: 87-106, 2000.
"Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats"
Tobias CA, Dhoot NO, Wheatley RA, Tessler A, Murray M, and Fischer I
J. Neurotrauma 18: 287-301, 2001.
"Transplants of cells genetically modified to express neurotrophin-3 (NT-3) rescue axotomized Clarke's nucleus neurons after spinal cord hemisection in adult rats"
Himes BT, Liu Y, Solowska JM, Fischer I, and Tessler A
J. Neurosci. Res. 65: 549-564, 2001.
"Intraspinal implants of fibrin glue containing glial cell line-derived neurotrophic factor promote dorsal root regeneration into spinal cord"
Iwakawa M, Mizoi K, Tessler A, and Itoh Y
Neurorehab. Neural Repair 15: 173-182, 2001.
"Transplantation of genetically modified fibroblasts expressing BDNF in adult rats with a subtotal hemisection improves some motor functions"
Kim D, Schallert T, Liu Y, Browarak T, Nayeri N, Tessler A, Fischer I, and Murray M
Neurorehab. Neural Repair 15: 141-150, 2001.
"Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury."
Jin Y, Fischer I, Tessler A and Houle JD
Exp. Neurol. 177: 265-275, 2002.
"Transplantation of genetically modified cells contributes to repair and recovery from spinal injury"
Murray M, Kim D, Liu Y, Tobias C, Tessler A, and Fischer I
Brain Res. Rev. 40: 292-300, 2002.
"Grafts of BDNF-producing fibroblasts that promote regeneration of axotomized rubrospinal neurons also rescue most neurons from retrograde death and prevent their atrophy"
Liu Y, Himes BT, Murray M, Tessler A, and Fischer I
Exp. Neurol. 178: 150-164, 2002.
"Patient selection for clinical trials: the reliability of the early spinal cord injury examination"
Burns AS, Lee BS, Ditunno JF, Tessler A
J. Neurotrauma 20(5):477-482, 2003.
Repair of chronic spinal cord injury"
Houle JD, Tessler A
Exp. Neurol. 182:247-260, 2003.
"Ex vivo MR apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF"
Schwartz ED, Shumsky JS, Wehrli S, Tessler A, Murray M and Hackney DB
Exp. Neurol. 182:49-63, 2003.
"Delayed grafting of BDNF and NT-3-expressing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy and provides limited regeneration"
Tobias CA, Shumsky JS, Shibata M, Tuszynski MH, Fischer I, Tessler A, Murray M
Exp. Neurol. 184:97-113, 2003.
"Spinal shock revisited: a four phase model"
Ditunno JF, Little JW, Burns AS, Tessler A
Spinal Cord 42:383-395, 2004.
"Towards a definition of recovery of function"
Murray M, Fischer I, Smeraski C, Tessler A, Giszter S
J. Neurotrauma 21:405-413, 2004.
"Immunosuppression with either cyclosporine A or FK506 promotes repair processes after spinal cord injury"
Hayashi Y, Shumsky JS, Connors T, Otsuka T, Fischer I, Tessler A, Murray M J. Neurotrauma. 22:1267-1281 2005.
Spontaneous potentials in distal muscles in animal models of spinal cord injury"
Burns AS, Lemay MA, Tessler A
Muscle and Nerve 31:46-51, 2005
"Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats"
Schwartz ED, Chin CL, Shumsky JS, Jawad AF, Brown BK, Wehrli S, Tessler A, Murray M and Hackney DB
Am. J. Neuroradiol. 26 (1): 7-18, 2005.
"Ex vivo evaluation of ADC values within spinal cord white matter tracts"
Schwartz ED, Cooper ET, Chin C-L, Wehrli S, Tessler A, Hackney DB
Am. J. Neuroradiol. 26 (2): 390-397, 2005
"Fate of immortalized human neuronal progenitor cells transplanted into rat spinal cord"
Li P, Tessler A, Han SSW, Fischer I, Rao MS, and Selzer ME
Arch. Neurol. 62: 223-229, 2005
"Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression"
Tobias CA, Han SSW, Shumsky JS, Kim D, Tumulo M, Dhoot NO, Wheatley MA, Fischer I, Tessler A and Murray M
J. Neurotrauma. 22: 138-156, 2005.
"Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury"
Park KI, Himes BT, Stieg PE, Tessler A, Fischer I, Snyder EY
Exp. Neurol. 199: 179-190, 2006.
"Paralysis elicited by spinal cord injury evokes selective disassembly of neuromuscular synapses with and without terminal sprouting in ankle flexors of the adult rat"
Burns AS, Jawaid S, Zhong H, Yoshihara H, Bhagat S, Murray M, Roy RR, Tessler A, Son J-Y
J. Comp. Neurol. 500: 116-133, 2007.
"Fibrillations following spinal cord injury: Improvement with neurotrophins and exercise"
Burns AS, Boyce VS, Tessler A and Lemay MA
Muscle and Nerve. 35: 607-613, 2007.
"Pathology of blast injury"
Kocsis J, Tessler A
J. Rehabil. Res. Dev. In Press. 2009.
Books and chapters in books (since 2000):
Saavedra, R. A., M. Murray, S. deLacalle and A. Tessler. 2000. In vivo neuroprotection of injured CNS neurons by a single injection of a DNA plasmid encoding the BCL-2 gene. Prog. Br. Res. 128: 365-372.
Liu, Y., M. Murray, A. Tessler and I. Fischer. 2000. Grafting of genetically modified fibroblasts into the injured spinal cord. Prog. Br. Res. 128: 309-319.
Himes, BT, and Tessler A. 2001. Neuroprotection from cell death following axotomy. In N.A. Ingoglia and M. Murray (eds.) Nerve Regeneration: New York: Marcel Dekker. pp. 477-504.
Selzer, ME, and Tessler A. 2000. Spinal cord regeneration. In E.G. Gonzalez, S.J. Myers, J.E. Edelstein, J.S. Lieberman and J.A. Downey (eds.) Downey and Darling’s Physiological Basis of Rehabilitation Medicine. 3rd Edition.: Woburn, MA. Pp. 629-662.
Ditunno, JF, AE Flanders, S Kirshblum, V Graziani and A Tessler 2002. Predicting outcome in traumatic spinal cord injury. In: S Kirshblum, DI Campagnolo and JA DeLisa (Eds.) Spinal Cord Medicine. Philadelphia: Lippincott Williams & Wilkins, pp. 108-122.
Tessler. A. 2004. Neurotrophic effects on dorsal root regeneration into the spinal cord. In: S. Mori, D.G. Stuart and M. Wiesendanger (Eds.), Brain Mechanisms for the Integration of Posture and Movement, Prog. Br. Res. Vol. 000, Amsterdam: Elsevier, pp. 147-154.
Fischer, I, AC Lepore, SSW Han and A Tessler. (2005) Cellular replacement in spinal cord injury. In: ME Selzer, S Clarke, LG Cohen, PW Duncan and FH Gage (Eds.) Textbook of Neural Repair and Rehabilitation. Cambridge: Cambridge University Press, pp. 445-467.