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118. Small Intestinal Submucosa for Anular Repair: Long Term Response in an In Vivo Sheep Model
Proceedings of the NASS 22nd Annual Meeting / The Spine Journal 7 (2007) 1S–163S 6
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Jeanette Libera , Jo¨rg Herdmann, MD , Olivera Josimovic-Alasevic, MD ; 1 North American Spine Society, Straubing, Bavaria, Germany; 2 Bergmannstrost, Halle, Saxony-Anhalt, Germany; 3Orthop. Department Mu`nchen-Harlaching, Munich, Bavaria, Germany; 4Oberlinhaus Potsdam, Potsdam, Brandenburg, Germany; 5Germany; 6Teltow, MecklenburgWestern Pomerania, Germany; 7Heinrich-Heine-Universita¨t Du¨sseldorf, Du¨sseldorf, Germany; 8Teltow, Germany BACKGROUND CONTEXT: The development of chronic back pain following lumbar disc herniation, especially after operative procedures, can not be avoided. However, so far no clinical procedure is available to slow down the progression of disc degeneration or to biologically replace the lost tissue. PURPOSE: To assess the clinical relevance of the autologous disc-derived chondrocyte transplantation (ADCT) for the regeneration of degenerated intervertebral discs by comparing sequestrectomy only with sequestrectomy followed by autologous disc chondrocyte transplantation using chondrotransplantÒDISC (co.don AG, Germany). STUDY DESIGN/SETTING: A multicenter, prospective, randomized, assessment-blinded, controlled clinical trial, the EuroDISC study, was initiated. PATIENT SAMPLE: 53 patients, 27 patients within the ADCT-treated group and 26 patients within the control group were assessed within the here presented subgroup analysis. OUTCOME MEASURES: As the primary parameter the Oswestry Low Back Pain Disability Questionnaire (PODQ)(according to Hudson-Cook) after one year was chosen; as secondary criteria the Quebec Back Pain Disability Scale (QBPD), Prolo scale, a VAS, MRI, x-rays and AE/SAE were used. METHODS: Patients 18 to 60 years of age requiring surgical intervention on one level between L3 and S1 were included. All patients were treated with a sequestrectomy. From patients included within the ADCT-treated group, the sequestrated disc tissue was used for disc chondrocyte isolation and their autologous propagation. 3 months later the disc-derived chondrocyte transplants were transplanted back into the operated discs nucleus region under fluoroscopic control and following integrity measurement of the anulus fibrosus. RESULTS: During the Follow up of 2 years, for the autologous discderived chondrocyte transplantation significant differences for the primary parameter OBPD as well as for the secondary parameter QBPD and VAS were found. For the ADCT-treated group, the total sumscore of the OPDQ decreased to 2 compared to the control group that only reached 6.5. The disability index of the OPDQ of the ADCT-treated group decreased to 4 compared to 13 for the group of patients that did not receive the autologous disc-derived chondrocyte transplants. The VAS decreased to 9 after ADCT treatment compared to a scaling of 15 for the control group patients that were only operated by sequestrectomy. CONCLUSIONS: The interims results of the EuroDISC study give strong evidence for the safety and efficiency of the disc-derived chondrocyte transplantation applied following sequestrectomy to delay or inhibit ongoing processes of disc degeneration. FDA DEVICE/DRUG STATUS: Autologous disc chondrocytes: Investigational/ Not approved. doi: 10.1016/j.spinee.2007.07.139
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success. An optimal treatment would restore the competency of the anulus and leave no residual implant for long term complications. Small intestinal submucosa (SIS) is a naturally occurring acellular, biodegradable, extracellular collagen-based material derived from the submucosa layer of the porcine small intestine. SIS has been shown to act as a resorbable scaffold in vivo that promotes host soft tissue regeneration and site-specific tissue remodeling. PURPOSE: To determine the efficacy of closing, repairing, and regenerating the anulus after anulotomy using an SIS based ‘‘patch and plug’’ scaffold. STUDY DESIGN/SETTING: 26 week in vivo animal study. PATIENT SAMPLE: Sheep. OUTCOME MEASURES: Plain radiographs, MRI, pressure testing, histology. METHODS: Following IACUC approval, 12 sheep underwent a retroperitoneal exposure of the lumbar spine. Three levels were assigned to undergo either: no additional procedure (exposure-only), a box anulotomy alone (anulotomy-only), or a box anulotomy followed by placement of an SIS ‘‘patch and plug’’ (SIS). At 26 weeks, spines were harvested for analysis. Spines from six animals (18 levels) underwent pressure-volume testing to assess the competency of the anulus. Spines from the remaining six animals (18 levels) had T1 and T2 weighted high resolution (3T MRI) images taken. Images were assessed for disc height, demarcation of nucleus, disc T2 signal intensity, and overall health/pathology of the disc. Undecalcified histologic specimens were evaluated for presence of fibrous tissue, evidence of inflammatory response, evidence of residual SIS, and degree of tissue organization. RESULTS: At six months post-operatively, the SIS was resorbed in all animals with no evidence of residual SIS present. Radiographs, MRI images, and histology all indicate that there was an exuberant tissue response at the SIS treated levels with both bone and fibrous tissue formation. Histologic analysis indicated that new tissue formation in anulotomy-only specimens was generally not accompanied by integration into the native anulus, whereas in SIS treated specimens, 75% had good integration between native anulus and new tissue. Discs treated with the SIS patch and plug exhibited a healing response both outside and within the margins of the anulus but new tissue formation did not resemble the organization of native anulus tissue. The degree of tissue regeneration was substantial enough to allow the disc to recover a mean 66% of its capacity to develop internal pressure. MRI images indicate that SIS treated levels did not maintain signal intensity comparable to exposure-only (intact) levels, but T2 signal intensity of SIS treated discs was statistically significantly higher than anulotomy-only levels. CONCLUSIONS: An important finding from this study is that the SIS treated discs were better able to maintain hydration relative to levels that did not receive SIS. SIS enhanced the healing response of the intervertebral disc relative to anulotomy-only levels. The SIS patch and plug can reduce the cascade of morphologic and functional degeneration that an intervertebral disc undergoes following anulotomy and partial discectomy. Further refinement of the SIS patch and plug is necessary to optimize repair of the anulus while minimizing osteophyte formation. FDA DEVICE/DRUG STATUS: Small Intestinal Submucosa: Not approved for this indication. doi: 10.1016/j.spinee.2007.07.140
118. Small Intestinal Submucosa for Anular Repair: Long Term Response in an In Vivo Sheep Model Eric Ledet, PhD1, Allen Carl, MD2, Joseph Glennon3, Winston Jeshuran, MD4, Patrick De Deyne, PhD5, Clifford Belden, MD6, Christopher Shaffrey, MD7; 1Troy, NY, USA; 2Albany, NY, USA; 3Capital District Veterinary Surgical Associates, Pattersonville, NY, USA; 4Albany Medical College, Albany, NY, USA; 5Raynham, MA, USA; 6NY, USA; 7 Charlottesville, VA, USA
119. The Effects of Lentiviral Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats Masashi Miyazaki, MD1, Osamu Sugiyama1, Benjamin Tow, MD1, Jun Zou, MD1, Yuichiro Morishita1, Feng Wei, MD1, Antonia Napoli1, Chananit Sintuu1, Jay R. Lieberman, MD1, Jeffrey C. Wang, MD1; 1 University of California, Los Angeles, Los Angeles, CA, USA
BACKGROUND CONTEXT: The incidence of reherniation following discectomy in the lumbar spine has been reported as high as 26%. Various techniques have been attempted to close the anulus, but with limited
BACKGROUND CONTEXT: Spinal arthrodesis is a commonly performed spinal procedure and autograft remains the standard for achieving spinal fusion. However, its procurement is associated with significant
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Jeanette Libera , Jo¨rg Herdmann, MD , Olivera Josimovic-Alasevic, MD ; 1 North American Spine Society, Straubing, Bavaria, Germany; 2 Bergmannstrost, Halle, Saxony-Anhalt, Germany; 3Orthop. Department Mu`nchen-Harlaching, Munich, Bavaria, Germany; 4Oberlinhaus Potsdam, Potsdam, Brandenburg, Germany; 5Germany; 6Teltow, MecklenburgWestern Pomerania, Germany; 7Heinrich-Heine-Universita¨t Du¨sseldorf, Du¨sseldorf, Germany; 8Teltow, Germany BACKGROUND CONTEXT: The development of chronic back pain following lumbar disc herniation, especially after operative procedures, can not be avoided. However, so far no clinical procedure is available to slow down the progression of disc degeneration or to biologically replace the lost tissue. PURPOSE: To assess the clinical relevance of the autologous disc-derived chondrocyte transplantation (ADCT) for the regeneration of degenerated intervertebral discs by comparing sequestrectomy only with sequestrectomy followed by autologous disc chondrocyte transplantation using chondrotransplantÒDISC (co.don AG, Germany). STUDY DESIGN/SETTING: A multicenter, prospective, randomized, assessment-blinded, controlled clinical trial, the EuroDISC study, was initiated. PATIENT SAMPLE: 53 patients, 27 patients within the ADCT-treated group and 26 patients within the control group were assessed within the here presented subgroup analysis. OUTCOME MEASURES: As the primary parameter the Oswestry Low Back Pain Disability Questionnaire (PODQ)(according to Hudson-Cook) after one year was chosen; as secondary criteria the Quebec Back Pain Disability Scale (QBPD), Prolo scale, a VAS, MRI, x-rays and AE/SAE were used. METHODS: Patients 18 to 60 years of age requiring surgical intervention on one level between L3 and S1 were included. All patients were treated with a sequestrectomy. From patients included within the ADCT-treated group, the sequestrated disc tissue was used for disc chondrocyte isolation and their autologous propagation. 3 months later the disc-derived chondrocyte transplants were transplanted back into the operated discs nucleus region under fluoroscopic control and following integrity measurement of the anulus fibrosus. RESULTS: During the Follow up of 2 years, for the autologous discderived chondrocyte transplantation significant differences for the primary parameter OBPD as well as for the secondary parameter QBPD and VAS were found. For the ADCT-treated group, the total sumscore of the OPDQ decreased to 2 compared to the control group that only reached 6.5. The disability index of the OPDQ of the ADCT-treated group decreased to 4 compared to 13 for the group of patients that did not receive the autologous disc-derived chondrocyte transplants. The VAS decreased to 9 after ADCT treatment compared to a scaling of 15 for the control group patients that were only operated by sequestrectomy. CONCLUSIONS: The interims results of the EuroDISC study give strong evidence for the safety and efficiency of the disc-derived chondrocyte transplantation applied following sequestrectomy to delay or inhibit ongoing processes of disc degeneration. FDA DEVICE/DRUG STATUS: Autologous disc chondrocytes: Investigational/ Not approved. doi: 10.1016/j.spinee.2007.07.139
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success. An optimal treatment would restore the competency of the anulus and leave no residual implant for long term complications. Small intestinal submucosa (SIS) is a naturally occurring acellular, biodegradable, extracellular collagen-based material derived from the submucosa layer of the porcine small intestine. SIS has been shown to act as a resorbable scaffold in vivo that promotes host soft tissue regeneration and site-specific tissue remodeling. PURPOSE: To determine the efficacy of closing, repairing, and regenerating the anulus after anulotomy using an SIS based ‘‘patch and plug’’ scaffold. STUDY DESIGN/SETTING: 26 week in vivo animal study. PATIENT SAMPLE: Sheep. OUTCOME MEASURES: Plain radiographs, MRI, pressure testing, histology. METHODS: Following IACUC approval, 12 sheep underwent a retroperitoneal exposure of the lumbar spine. Three levels were assigned to undergo either: no additional procedure (exposure-only), a box anulotomy alone (anulotomy-only), or a box anulotomy followed by placement of an SIS ‘‘patch and plug’’ (SIS). At 26 weeks, spines were harvested for analysis. Spines from six animals (18 levels) underwent pressure-volume testing to assess the competency of the anulus. Spines from the remaining six animals (18 levels) had T1 and T2 weighted high resolution (3T MRI) images taken. Images were assessed for disc height, demarcation of nucleus, disc T2 signal intensity, and overall health/pathology of the disc. Undecalcified histologic specimens were evaluated for presence of fibrous tissue, evidence of inflammatory response, evidence of residual SIS, and degree of tissue organization. RESULTS: At six months post-operatively, the SIS was resorbed in all animals with no evidence of residual SIS present. Radiographs, MRI images, and histology all indicate that there was an exuberant tissue response at the SIS treated levels with both bone and fibrous tissue formation. Histologic analysis indicated that new tissue formation in anulotomy-only specimens was generally not accompanied by integration into the native anulus, whereas in SIS treated specimens, 75% had good integration between native anulus and new tissue. Discs treated with the SIS patch and plug exhibited a healing response both outside and within the margins of the anulus but new tissue formation did not resemble the organization of native anulus tissue. The degree of tissue regeneration was substantial enough to allow the disc to recover a mean 66% of its capacity to develop internal pressure. MRI images indicate that SIS treated levels did not maintain signal intensity comparable to exposure-only (intact) levels, but T2 signal intensity of SIS treated discs was statistically significantly higher than anulotomy-only levels. CONCLUSIONS: An important finding from this study is that the SIS treated discs were better able to maintain hydration relative to levels that did not receive SIS. SIS enhanced the healing response of the intervertebral disc relative to anulotomy-only levels. The SIS patch and plug can reduce the cascade of morphologic and functional degeneration that an intervertebral disc undergoes following anulotomy and partial discectomy. Further refinement of the SIS patch and plug is necessary to optimize repair of the anulus while minimizing osteophyte formation. FDA DEVICE/DRUG STATUS: Small Intestinal Submucosa: Not approved for this indication. doi: 10.1016/j.spinee.2007.07.140
118. Small Intestinal Submucosa for Anular Repair: Long Term Response in an In Vivo Sheep Model Eric Ledet, PhD1, Allen Carl, MD2, Joseph Glennon3, Winston Jeshuran, MD4, Patrick De Deyne, PhD5, Clifford Belden, MD6, Christopher Shaffrey, MD7; 1Troy, NY, USA; 2Albany, NY, USA; 3Capital District Veterinary Surgical Associates, Pattersonville, NY, USA; 4Albany Medical College, Albany, NY, USA; 5Raynham, MA, USA; 6NY, USA; 7 Charlottesville, VA, USA
119. The Effects of Lentiviral Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats Masashi Miyazaki, MD1, Osamu Sugiyama1, Benjamin Tow, MD1, Jun Zou, MD1, Yuichiro Morishita1, Feng Wei, MD1, Antonia Napoli1, Chananit Sintuu1, Jay R. Lieberman, MD1, Jeffrey C. Wang, MD1; 1 University of California, Los Angeles, Los Angeles, CA, USA
BACKGROUND CONTEXT: The incidence of reherniation following discectomy in the lumbar spine has been reported as high as 26%. Various techniques have been attempted to close the anulus, but with limited
BACKGROUND CONTEXT: Spinal arthrodesis is a commonly performed spinal procedure and autograft remains the standard for achieving spinal fusion. However, its procurement is associated with significant