Faculty Book

MARY BARTLETT BUNGE, PH.D.
Christine E. Lynn Distinguished Professor in Neuroscience
Professor, Cell Biology & Anatomy, Neurological Surgery and Neurology

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Development of combination strategies to repair the injured spinal cord

Research Interests

The goal in my laboratory is primarily to foster regeneration of axons across and beyond the area of injury. This has been an objective since moving to Miami in 1989. To improve regeneration of axons after spinal cord injury, we are investigating increases in cyclic AMP levels, interference with proteoglycans (molecules that inhibit axonal growth), transplantation of Schwann cells and/or olfactory ensheathing glia, and genetic engineering of these cells before transplantation to improve their neurotrophic factor-secreting capability. We have also initiated a new microarray study to explore gene differences between neurons that are able to regrow onto a cellular bridge placed in the area of injury and those that do not grow onto the bridge. Because the reactions of the tissue to spinal cord injury are many and varied, I espouse the concept that a combination strategy will be necessary to adequately improve outcome after spinal cord injury.

A main contribution of my laboratory has been to introduce the novel use of a cellular (Schwann cell) bridge across a complete transection gap in the adult rat spinal cord. We have tried a number of combination strategies, and the spinal cord injured animal has improved. For example, when neurotrophins, brain-derived neurotrophic factor and neurotrophin-3, are introduced along with Schwann cell bridges, there are more regrowing fibers on the bridge and there is an increased variety of fibers on the bridge, including some from distant neuronal somata positioned in the brain stem. Fibers also exit the bridge after a combination strategy, such as the transplantation of olfactory ensheathing glia at either end of the Schwann cell bridge. This combination also led to long-distance axonal regeneration in the adult rat spinal cord. We also have tested combination strategies in a spinal cord contusion model. We have demonstrated that a combination strategy with either lesion model is consistently more effective than transplanting Schwann cells alone.  Also, more recent studies have been initiated to assess transplanted Schwann cell survival, and how to improve it, and to investigate modes of presenting the Schwann cells in the spinal cord from a bioengineering perspective.

Video Introduction

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Selected Publications

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Golden KL, Pearse DD, Blits B, Garg M, Oudega M, Wood PM, Bunge MB (2007) Transduced Schwann cells promote axon growth and myelination after spinal cord injury. Exp Neurol. 207:203-217.

Hill CE, Hurtado A, Blits B, Bahr BA, Wood PM, Bunge MB (2007) Early necrosis and apoptosis of Schwann cells transplanted into the injured rat spinal cord. Europ J Neurosci. 26:1433-1445.

Lane MA, Truettner JS, Brunschwig J-P, Gomez A, Bunge MB, Dietrich WD, Dziegielewska KM, Ek CJ, VandeBerg JL, Saunders NR (2007) Age-related differences in the local cellular and molecular responses to injury in developing spinal cord of the opossum, Monodelphis domestica.  Europ J Neurosci 25:1725-1742.

Pearse DD, Sanchez AR, Pereira FC, Andrade CM, Puzis R, Pressman Y, Golden KL, Kitay BM, Blits B, Wood PM, Bunge MB (2007) Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: survival, migration, axon association and functional recovery, Glia 55:976-1000.

Wanner IB, Mahoney J, Jessen KR, Wood PM, Bates M, Bunge MB (2006) Invariant mantling of growth cones by Schwann cell precursors characterize growing peripheral nerve fronts. Glia 54:424-438.

Casella GT, Bunge MB, Wood PM (2006) Endothelial cell loss is not a major cause of neuronal and glial cell death following contusion injury of the spinal cord. Exp Neurol. 202:8-20.  (Illustration on cover)

Moon LDF, Leasure JL, Gage FH, Bunge MB (2006) Motor enrichment sustains hindlimb movement recovered after spinal cord injury and glial transplantation.  Rest Neurol Neurosci
24:147-161.

Hill CE, Moon LDF, Wood PM, Bunge MB (2006) Labeled Schwann cell transplantation: Cell loss, host Schwann cell replacement and strategies to enhance survival.  Glia 53:338-343.

Blits B, Kitay BM, Farahvar A, Caperton CV, Dietrich WD, Bunge MB (2005) Lentiviral vector-mediated transduction of neural progenitor cells before implantation into injured spinal cord and brain to detect their migration, deliver neurotrophic factors and repair tissue. Rest Neurol Neurosci 23:313-324.      

Cao Q, Xu X-M, DeVries WH, Enzman GU, Ping P, Tsoulfas P, Wood PM, Bunge MB, Whittemore SR (2005) Functional recovery in traumatic spinal cord injury after transplantation of multineurotrophin-expressing glial-restricted precursor cells. J Neurosci 25:6947-6957.

Barakat DJ, Gaglani SM, Neravetla SR, Sanchez AR, Andrade CM, Pressman Y, Puzis R, Garg MS, Bunge MB, Pearse DD (2005) Survival, integration and axon growth support of glia transplanted into the chronically contused spinal cord. Cell Transplantation 14:225-240.

Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD (2005) Combining Schwann cell bridges and olfactory ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal  cord.  J Neurosci 25:1169-1178.

Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, Filbin M, Bunge MB (2003) Elevation of cyclic AMP enhances regeneration and improves behavioral recovery in Schwann cell-grafted animals after spinal cord injury

Bunge MB, Pearse DD (2003) Transplantation strategies to promote repair of the injured spinal cord. J Rehab Res Dev 40

Blits B, Oudega M, Boer GJ, Bunge MB, Verhaagen J (2003) Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hindlimb function. Neuroscience 118:271-281.

Takami T, Oudega M, Bates ML, Wood PM, Kleitman N, Bunge MB (2002) Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord . J Neurosci 22:6670-6681.

Bunge MB (2001) Bridging areas of injury in the spinal cord. Neuroscientist 7:325-339.

Plant GW, Bates ML, Bunge MB (2001) Inhibitory proteoglycan immunoreactivity is higher at the caudal than the rostral Schwann cell graft-transected spinal cord interface. Molec Cell Neurosci 17:471-487.

Ramón-Cueto A, Plant GW, Avila J and Bunge MB (1998) Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci 18:3803-3815. [Abstract]

 

Last updated October, 2007

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