Cellular transplants for spinal cord repair. Development of combinatorial spinal cord repair strategies.
An injury to the spinal cord results in immediate death of neural cells, severance of axons, and loss of motor and sensory function. In time, more tissue is lost due to a cascade of destructive physiological events. Because endogenous repair mechanisms fail to repair the spinal cord anatomically or functionally the loss of function is permanent. There are no treatments available that restore function in a manner that an independent life can be lived. Thus the current prognosis for spinal cord injured persons is to spend the remainder of their life in a wheelchair. However, progress is being made in the laboratory that warrant hope for the development of effective (combination) repair strategies for the spinal cord.
Dr. Oudega's research interest is the potential of cellular and a-cellular transplants to reduce secondary injury (limit additional tissue loss), promote axonal regeneration, and increase motor and sensory outcome after spinal cord injury. In his laboratory, adult rat spinal cord injury model systems are employed to test the reparative abilities of transplants alone or in combination with other growth-supporting interventions such as increasing the levels of growth-promoting factors or decreasing the activity of naturally present growth-inhibitory factors. Studies especially focus on the repair efficacy of Schwann cells, bone marrow stromal cells, and a-cellular biomaterials. Viral vectors are frequently used to modify cells prior to transplantation and/or the spinal cord environment nearby the intraspinal transplant. The repair efficacy of interventions that decrease the level or activity of naturally present growth-inhibitors is also a research focus in Dr. Oudega's laboratory especially in the context of axonal growth from an intraspinal graft into the adjacent spinal cord tissue. He also employs a zebrafish spinal cord injury model to elucidate genes that are crucial for the failure or success of axon regeneration after spinal cord injury.
The overall goal of Dr. Oudega's Spinal Cord Repair Laboratory is to develop strategies that result in significant axonal regeneration and functional restoration after spinal cord injury and to translate these approaches into the clinical arena.
Nandoe Tewarie, D.S., Hurtado, A., Bartels, R.H.M.A., Grotenhuis, A. and Oudega, M. Stem-cell based therapies for spinal cord injury. J Spin Cord Med. 32(2): 105-114, 2009.
Oudega, M. Schwann cells and olfactory ensheathing cell implantation for repair of the contused spinal cord. Acta Physiol (Oxf). 189(2): 181-189, 2007.
Hill, C.E., Hurtado, A., Blits, B., Bahr, B., Wood, P.M., Bunge, M.B. and Oudega, M. Early necrosis and apoptosis of Schwann cells transplanted into the moderately contused adult rat spinal cord. Eur J Neurosci. 26: 1422-1445, 2007.
Hurtado, A., Moon, L.D.F., Maquet, V., Blits, B., Jérôme, R. and Oudega, M. Poly (D,L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete a bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord. Biomaterials. 27(3): 430-442, 2006.
Nandoe, R.D.S., Hurtado, A., Levi, A.D.O., Grotenhuis, A. and Oudega, M. Bone marrow stromal cell for repair of the spinal cord: towards clinical application. Cell Transpl. 15: 563-577, 2006.