Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model.
BACKGROUND
Lumbar discectomies are common surgical interventions that treat radiculopathy by removing herniated and loose intervertebral disc (IVD) tissues. However, remaining IVD tissue can continue to degenerate resulting in long-term clinical problems. Little information is available on the effects of discectomy on IVD biology. Currently, no treatments exist that can suspend or reverse the degeneration of the remaining IVD.


OBJECTIVE
To improve the knowledge on how discectomy procedures influence IVD physiology and to assess the potential of growth factor treatment as an augmentation during surgery.


METHODS
To determine effects of discectomy on IVDs with and without transforming growth factor beta 3 (TGFβ3) augmentation using bovine IVD organ culture.


METHODS
This study determined effects of discectomy with and without TGFβ3 injection using 1-, 6-, and 19-day organ culture experiments. Treated IVDs were injected with 0.2 μg TGFβ3 in 20 μL phosphate-buffered saline+bovine serum albumin into several locations of the discectomy site. Cell viability, gene expression, nitric oxide (NO) release, IVD height, aggrecan degradation, and proteoglycan content were determined.


RESULTS
Discectomy significantly increased cell death, aggrecan degradation, and NO release in healthy IVDs. Transforming growth factor beta 3 injection treatment prevented or mitigated these effects for the 19-day culture period.


CONCLUSIONS
Discectomy procedures induced cell death, catabolism, and NO production in healthy IVDs, and we conclude that post-discectomy degeneration is likely to be associated with cell death and matrix degradation. Transforming growth factor beta 3 injection augmented discectomy procedures by acting to protect IVD tissues by maintaining cell viability, limiting matrix degradation, and suppressing NO. We conclude that discectomy procedures can be improved with injectable therapies at the time of surgery although further in vivo and human studies are required.
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Svenja
S
Illien-Jünger
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Young
Y
Lu
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Devina
D
Purmessur
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Jillian E
JE
Mayer
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Benjamin A
BA
Walter
Genetics Unit, Shriners Hospital, 1529 Cedar Avenue, Montreal, Quebec H3G1A6, Canada.
Peter J
PJ
Roughley
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Sheeraz A
SA
Qureshi
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA.
Andrew C
AC
Hecht
Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1188, New York, NY 10029, USA. Electronic address: james.iatridis@mssm.edu.
James C
JC
Iatridis
D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects*; D004195:Disease Models, Animal; D017586:Diskectomy / Q000009:adverse effects*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology / Q000627:therapeutic use*
D053674:Aggrecans; D011509:Proteoglycans; D053782:Transforming Growth Factor beta3; D009569:Nitric Oxide
Discectomy; Growth factor; Herniation; Intervertebral disc; Organ culture; TGFβ3