Focus of Studies

The Drexel University College of Medicine Center uses sophisticated methods of modern molecular biology, cell and tissue transplantation and robotics to develop innovative strategies and rehabilitative techniques for the treatment of spinal cord injury. The effects of these treatments on recovery of function are carefully monitored by neurophysiological and behavioral analysis of motor, sensorimotor and autonomic functions that are severely impaired in injured patients.

Previous Achievements:

 1. Pioneering studies conducted over 20 years ago revealed the remarkable capacity of uninjured nerve cells to compensate for the loss of those destroyed by injury. The insights that came from these studies provide some of the explanations for beneficial effects of treatments and supply part of the rationale for current intensive rehabilitative techniques employed in the treatment of spinal cord injury.

 2. Experiments carried out within the last two decades were among the first to use transplants, initially of fetal spinal cord and then of genetically modified fibroblasts (skin cells) to treat experimental spinal cord injury. These studies led to important insights into the mechanisms by which transplants could assist in the recovery of locomotion. These studies demonstrated:

• Fetal transplants helped some types of nerve cells to regenerate their axons after spinal cord injury.
• Regeneration was especially vigorous when transplants were placed into the injured spinal cords of young rats.
• Robust regeneration can be induced in the adult without fetal transplants by supplying growth factors using gene therapy strategies.
• Transplants of genetically modified cells are protected from immunological rejection by capsules that selectively allow delivery of the secreted product.
• Grafting of multipotent neural stem cells combined with gene therapy allows delivery of therapeutic products and continued differentiation of these cells.
• Neuronal-restricted precursors and glial-restricted precursors become neurons and glial cells when transplanted into the spinal cord.
• Transplants of bone marrow stromal cells into injured spinal cord produces a permissive environment that allows robust growth of axons.
• Transplant rescued injured nerve cells in the spinal cord and brain that die in the absence of a transplant.
• Transplants rescue neurons because they supply specific growth factors that are essential for survival.
• Analysis of the locomotion of normal and injured animals confirmed quantitatively that transplants improved the walking of newborn rats after spinal cord injury.
• Animals with transplants walked even better when transplants were combined with drugs that mimic the actions of specific neurotransmitter substances that are depleted by injury.
• Analysis of bladder function in normal and injured animals confirmed quantitatively that transplants improved function and that function could further be improved when combined with drugs that mimic specific neurotransmitters.
• Combining transplants and pharmacological agents to obtain a better outcome opens exciting possibilities for treatment of patients with spinal cord injury including recovery of bladder function, reduction of neuropathic pain and improved motor function.
• Exercise of injured limbs is designed to re-train regions of the spinal cord that have been separated from descending input from the brain. There is strong evidence of activity dependent plasticity within the brain and spinal cord after exercise which we aim to translate into greater behavioral recovery.
• modulation of glial scar tissue breaches a major structural/chemical barrier to growth in the injured spinal cord

Current Research

Although fetal transplants have shown great promise in the treatment of spinal cord injury, the use of fetal human tissue in patients would be extremely controversial and not always practical because of the limited and unpredictable availability of healthy donor tissue. Therefore the Drexel University College of Medicine (DUCOM) Center has undertaken a series of studies to evaluate promising candidate cells and genetic engineering to design more efficacious and more practical types of transplants combined with delivery of therapeutic products. These cells can be grown in tissue culture and stored, so they can be available when needed. Some types of the cells, such as skin fibroblasts and bone marrow cells, might be taken from the patients themselves, others, such as neural stem cells, have the potential to be used for cell replacement. For example, the DUCOM researchers have genetically engineered fibroblast cells to express growth factors that previous experiments suggested were important for the rescue and regeneration of injured spinal cord and brain nerve cells. When these genetically modified cells were transplanted into the damaged spinal cord of adult rats, the cells were as effective as fetal transplants in rescuing injured neurons. In a recent study they used sensitive quantitative tests to show that the genetically modified cells promoted regeneration of injured brain neurons and recovery of limb use that exceeded that seen with fetal transplants.

Physiological and bioengineering experiments are identifying the spinal and supraspinal mechanisms that support the recovered movements. Some interventions may act independently of those recovery mechanisms that result from transplant-mediated modifications of circuitry. Pharmacological interventions that act to replace lost transmitter systems enhance recovery from spinal injury and act synergistically with transplant mediated changes in circuitry to further improve function. Rehabilitative therapies that may act in concert with both pharmacological and transplant mediated mechanisms are activity dependent mechanisms that may improve specific motor functions. As the time draws nearer for translation of these findings into clinical practice, clinical colleagues in Neurology, Orthopedics, Neurosurgery, Rehabilitation, and Radiology Departments at DUCOM, Jefferson, The Shriners Hospital for Children and University of Pennsylvania are collaborating in developing preclinical approaches to the evaluation and treatment of spinal injury. Our goal is to bridge the gap between the discovery phase and clinical application by optimizing promising research strategies and developing effective protocols to treat patients whose function has been limited by spinal cord injury..