UT/Rhodes Neurosurgery Research Fellowship 2008 Faculty
Laboratory Emphasis:
Karen A. Hasty, PhD
Wilhelm Professor of Orthopaedic Surgery, Campbell Clinic, UT Health Science Center, VA Medical Center
Research group description. Students will be expected to work with an interdisciplinary team of cell biologists, spine surgeons and biomedical engineers in a combined approach to arrest intervertebral disc degeneration. The techniques that this team uses involve tissue culture of damaged intervertebral specimens, molecular biology, disc surgery on an animal model, tissue engineering and histopathology. Co-authorship on publications will be offered for any significant input on the project.
Summary of the experimental design.Arresting progression of intervertebral disc (IVD) degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. My laboratory research will test a therapeutic approach for intervening early in the degenerative process. We will determine the effects of platelet-rich plasma (PRP), a natural source of many growth factors) on the gene expression of human intervertebral disc tissues surgically removed from patients with herniated discs. The IVD tissues will be cultured in vitro with the PRP, then the cells will be extracted for RNA and the expression of the extracellular matrix components, types I, II collagens and aggrecan, and the transforming growth factors beta 1&3 as well as the matrix metalloproteinases (MMP), MMP-1 and MMP-13, will be measured by quantitative RT-PCR. We expect that expression of the extracellular matrix (ECM) components and the growth factors that stimulate ECM will be increased in cells stimulated with PRP, a beneficial effect for a tissue where the ECM functions to resist mechanical stress. By contrast, we expect that the levels of MMPs, the enzymes that degrade ECM will be decreased. This would be a positive result as the ECM would be preserved. To determine if this therapy could be clinically used for injection of damaged discs in patients to prevent surgical removal, we will use a porcine model of surgically induced disc degeneration to determine the in vivo effects of an intranuclear injection of platelet-rich plasma on the metabolism of a damaged IVD, For some injured discs, tissue engineered replacement discs will also be implanted. After injection and stabilization of the animals for 1-3 months, tissues will be removed for analyses of gene expression and processed for microscopic examination of the experimentally treated discs compared to the untreated controls. Changes in MRI status of the injected disc will be monitored.
Clinical significance. All adult degenerative spine pathologies (herniated disc, degenerative spondylolisthesis, lateral recess stenosis) are different points on the same degenerative spectrum. If we can intervene in the pathological pathways upregulated during this process and suppress them, we may be able to slow, or even prevent, the adult degenerative spine cascade. We would no longer deal with the degenerative spine after the damage has been done but rather try to prevent the damage from occurring. This would allow us to slow or stop progression of degerative disc disease in a low cost minimally invasive outpatient environment thereby preventing its deleterious effects.
Potential clinical strategies. If we successfully downregulate the production of destructive factors in the intervertebral disc, our first subjects would involve patients undergoing traditional microscopic lumbar discectomy. These patients have an early stage degenerative disc and will have an annulotomy for access to the disk. Application of a bioengineered substance at this stage may stimulate disc healing and prevent further disc degeneration. If this proves successful, we would expand our indications to patients undergoing discograms who are being evaluated for lumbar fusions. By injecting painful discs, we hope to stimulate healing and prevent some of these patient from undergoing an irreversible fusion
Clinical Emphasis:
Frederick A. Boop, MD
Chief, Division of Pediatric Neurosurgery
LeBonheur Children′s Hospital
Associate Professor, Department of Neurosurgery
The University of Tennessee College of Medicine
The pediatric neurosurgery program at LeBonheur Children′s Hospital is one of the busiest in the country, having performed 760 pediatric neurosurgical operations last year. Our neuroscience program provides care for children over a 5 state area here in the mid-South. We also draw patients from across the country and from around the world. We have two neuroscience programs that are nationally recognized. First, our pediatric brain tumor program, a joint program with St Jude, is one of the largest in the country, having performed 160 operations for tumor last year. Secondly, our pediatric epilepsy program is also nationally acclaimed. Students wishing to participate in this program would be expected to make teaching rounds with us, come to the operating room to observe neurosurgical procedures, assist in a clinical project which we would hope would culminate in a peer reviewed publication in which they would be listed as co-author, and attend our neurosurgical teaching conferences during the week. If students were interested in shadowing a resident during night call, this could also be arranged. I would anticipate an 8 week rotation, but this could be extended if the student wished. The hours can be quite flexible, making accommodation for summer family vacation, etc.
