- Email: [email protected]
52. Effects of Chronic Cyclic Loading on the Lumbar Spine: An In Vivo Pilot Study
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Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S-205S
similar to pre-operative and comparable to that in patients undergoing lumbar surgery at 1.5 years. Smoking, COPD, and female gender are possible factors in the development of post-operative dysphagia. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
51. Effect of a Novel Bioscaffold on DBM in an Athymic Rat Spinal Fusion Model William Lloyd, BS1, Michael Larson2, Ronald Hill3; 1Pioneer Surgical, Greenville, NC, USA; 2Ibex Preclinical Research Inc, Logan, UT, USA; 3 Greenville, NC, USA
doi: 10.1016/j.spinee.2009.08.060
BACKGROUND CONTEXT: Recent studies suggest that variable responses to DBM may result from differing levels of retained BMP’s and other factors. A previous study demonstrated that a novel bioscaffold composed of denatured collagen and a high molecular weight dextran (E-Matrix) significantly enhanced the BMP-2 effect on posterior lateral fusion in a rat model. This study was undertaken to determine the effect of E-Matrix on human DBM in posterior lateral fusion. PURPOSE: The purpose of this study was to determine whether E-Matrix improves the consistency of the response to DBM bone grafts and improves spinal fusion results. STUDY DESIGN/SETTING: Animal model (in vivo). PATIENT SAMPLE: 22 Athymic Sprague-Dawley rats. OUTCOME MEASURES: Fusion by manual palpation, radiography and histopathology. METHODS: This study compared: a commercially available human DBM bone graft; a bone graft consisting of human DBM, a novel bioscaffold carrier composed of denatured collagen and dextran (E-Matrix) and nanocrystalline hydroxyapatite granules (E-Matrix/nano DBM); and allograft in an athymic rat posterior-lateral spinal fusion model. Animals were randomly assigned to the three treatment groups: allograft (N56), commercial DBM (N58), or E-Matrix/nano DBM (N58). The test or control article was placed bilaterally (0.3 ml per side) over and between the decorticated transverse processes between the L4 and L5 vertebrae. Radiographs were taken immediately after surgery and at the 8 week termination. Bilateral fusion was assessed by manual palpation performed by 2 independent observers blinded to treatment group and by histopathology. Statistical comparisons were made using a one-way ANOVA and SNK procedure as appropriate. RESULTS: Both the commercial DBM and E-Matrix/nano DBM resulted in 100% fusion (16/16 sites, 8 animals each) by manual palpation compared to only 2/12 sites (6 animals) in the allograft control. Similar findings were noted in the radiographic analysis. However, the histological results revealed that E-Matrix/nano DBM resulted in a statistically significant increase in the percentage of new bone filling the implant site between the transverse processes compared to commercial DBM or allograft (84 6 7%, 38 6 10% and 12 6 7% respectively, mean 6 sem, p!0.05). E-Matrix/nano DBM resulted in a statistically greater tissue response score (Regenerative Degenerative Tissue Responses) compared to the other treatment groups: 8.7 6 0.6, 5.4 6 1.0, and 3.4 6 0.9 respectively (mean 6 sem, p!0.05). CONCLUSIONS: E-Matrix/nanoss DBM resulted in an improved tissue response, greater bone formation, and less variability in these responses compared to a commercially available DBM and allograft controls. This improved spinal fusion response is analogous to previously published data demonstrating fusion at lower concentrations of BMP2 when mixed with E-Matrix in a rat model. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
Wednesday, November 11, 2009 5:10–6:10 PM Focused Paper Presentations 3: Basic Science 50. Transplantation of Bone Mesenchymal Stem Cells Reduced Plasma Adrenocorticotropic Hormone Content in Rats with Spinal Cord Injury: A Potential Anti-Chronic Stress Mechanism Jun Zhou, MD, PhD1, Huilin Yang, MD, PhD1, Jie Ding, MD, PhD2, Jiannong Cen, PhD3, Zhenjiang Li, PhD3; 1The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; 2Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Jiangsu Institute of Hematology, Suzhou, Jiangsu, China BACKGROUND CONTEXT: Recent studies have demonstrated potential therapeutic effects of bone mesenchymal stem cells (BMSCs) to spinal cord injury (SCI) in rat model. However, the exact mechanism is still unknown. The authors investigated a potential anti-chronic stress mechanism of BMSCs transplantation for rat SCI. PURPOSE: To investigate a potential anti-chronic stress mechanism of transplanted BMSCs for rat SCI. STUDY DESIGN/SETTING: Experimental spinal cord injury using a rat model. PATIENT SAMPLE: No patients were enrolled in this study. OUTCOME MEASURES: N/A. METHODS: A total of 48 adult male SD rats were divided into 3 groups randomly: control, model and treatment group, n516 in every group. Rats in model and treatment group were performed a partial low thoracic SCI by modified Allen’s method at T10. Rats in ontrol group received only laminectomy. At day 7 After SCI, the dura at L4-L5 intervertebral space was exposed; 100 l of Hank’s buffered saline solution contained 1 million rat BMSCs or the same amount of Hank’s buffered saline solution was injected into the subarachnoid space. Evaluated hind limb motor function by Basso, Beattie and Bresnahan (BBB) scale pre-injection and at day 14, 28 post-injection. Half of rats in every group were anesthetized at day 14, 28 post-injection, collected blood for detection of plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT) content by enzyme linked immunosorbent assay (ELISA). RESULTS: At day 3, 7 days after surgery, BBB scale score of rats in model and treatment group was lower than control group (p!0.01). After transplantation of BMSCs, BBB scale score of rats in treatment group increased progressively, higher than those in model group at day 14, 28 post-injection, but still lower than control group (p!0.01). At day 14 post-injection, the plasma ACTH content in model group were higher than control group (p!0.05);but there was no significant difference in serum CORT content between the three groups. At day 28 post-injection, the plasma ACTH content in model group were higher than treatment group (p!0.05), and the serum CORT content in model group were higher than control group (p!0.05). CONCLUSIONS: BMSCs transplantation could improve the hindlimb motor function of SCI rats, reduce plasma ACTH content, which implied a potential anti-chronic stress mechanism of transplanted BMSCs for rat SCI. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. doi: 10.1016/j.spinee.2009.08.062
doi: 10.1016/j.spinee.2009.08.063
52. Effects of Chronic Cyclic Loading on the Lumbar Spine: An In Vivo Pilot Study Glenn Sanders1, Sarah Linley1, Daniel Ramsey1, Rosalyn Abbott1, J. Puzas2, Joseph Glennon3, Darryl DiRisio, MD4, James Lawrence4, Allen Carl, MD4, Eric Ledet, PhD5; 1Rensselaer Polytechnic Institute, Troy, NY, USA; 2Rochester, NY, USA; 3Capital District Veterinary Surgical Associates, Pattersonville, NY, USA; 4Albany Medical College, Albany, NY, USA; 5Troy, NY, USA BACKGROUND CONTEXT: Epidemiologic data indicate a correlation between cyclic axial compression and degenerative disc disease (DDD)
Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S-205S in the lumbar spine. Clinically, endplate sclerosis is often observed concomitant to DDD; however, the relationship between cyclic loading, endplate sclerosis, and DDD is uncharacterized. Repeated mechanical loading may initiate subchondral sclerosis, which subsequently diminishes diffusion to and from the disc, ultimately leading to DDD. PURPOSE: The purpose of this study was to characterize the temporal effects of in vivo chronic cyclic compression on: disc height, diffusion, subchondral sclerosis, and disc morphology in the lumbar spine. STUDY DESIGN/SETTING: New Zealand white rabbits underwent loading of the lumbar spine. PATIENT SAMPLE: New Zealand white rabbits. OUTCOME MEASURES: N/A. METHODS: New Zealand white rabbits underwent a surgical procedure where pins were placed transversely through the L4 and L5 vertebrae. Four percutaneous posts, extending dorsally from the vertebrae, were attached to the pins to facilitate manipulation of the vertebrae from an external apparatus. A novel external load frame was used to apply daily cyclic axial compression to the conscious animals. Forces equivalent to 5 x BW were applied at one of two physiologically relevant frequencies. Cyclic compression was applied 2 hrs/day, 5 days/week, for 6 months. Radiographs were taken every two weeks throughout the study to assess changes in disc height and to monitor onset of sclerosis. After 6 months of loading, rabbits were administered gadolinium, euthanized and MR imaged to assess diffusion and disc morphology. MicroCT analysis was conducted to quantify changes in subchondral bone density. Morphologic changes of the disc, endplate, and subchondral bone were assessed via histology. RESULTS: Animals in the high frequency group underwent up to 2.2 million loading cycles. Plain radiographs indicated no discernable loss of disc height in both frequency groups. However, there was evidence of sclerotic changes and osteophyte formation at loaded levels. T1 and T2-weighted MR images showed no consistent pattern of signal change at loaded levels compared to the adjacent levels, however the resolution of MRI was poor for assessing the small discs. MicroCT analysis revealed a consistent increase in subchondral bone density at loaded levels compared to adjacent control levels, as shown in the Figure. CONCLUSIONS: We have developed a novel in vivo model for studying the effects of cyclic loading on the intervertebral disc, endplate, and subchondral bone. This model can be utilized to characterize the mechanism of pathology and its dependence on factors such as load magnitude, frequency, and duration. In this pilot study, our data indicate that plain radiographs and MRI – two clinically relevant diagnostic measures – did not detect early morphologic changes to the disc in response to repeated cyclic loading at physiologic magnitudes and frequencies. However, there was evidence of sclerotic changes to the subchondral bone and osteophyte formation in response to these loads. This finding is significant in that subchondral sclerosis has previously been shown to impede diffusion to and from the intervertebral disc, ultimately initiating or exacerbating disc degeneration. Our data indicate that subchondral sclerotic changes occur in response to repeated cyclic axial loading, suggesting a mechanism linking repeated mechanical loading to DDD.
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53. Transplantation of Goat Bone Marrow-Derived Stromal Cells to a Degenerative Intervertebral Disc in a Goat Disc-Injury Model Yejia Zhang, MD, PhD1, Susan Drapeau, PhD2, Howard An, MD3, Eugene Thonar, PhD3, D Greg Anderson, MD4; 1Rush University Medical Center, Chicago, IL, USA; 2Memphis, TN, USA; 3Chicago, IL, USA; 4 Rothman Institute, Philadelphia, PA, USA BACKGROUND CONTEXT: Disc injury models in small animals have disadvantages: the small disc size makes it difficult to inject adequate volumes for tissue engineering studies and the persistence of notochordal cells within the small animal discs limit their applicability as a model for human disc degeneration. The goat was selected because its intervertebral discs (IVDs) are similar in shape and in size to human discs. Bone marrow stromal cells were used because they are free of ethical concerns related to embryonic stem cells. PURPOSE: This is a pilot study to examine the effects of bone marrow stromal cells (BMSC) on degenerating IVDs in the goat. STUDY DESIGN/SETTING: This is a basic science study using a goat disc degeneration model to examine the effects of bone marrow-derived stem cells on degenerating discs. PATIENT SAMPLE: N/A. OUTCOME MEASURES: The biochemical composition of the NP. METHODS: Twenty-four goats (4 years-old) were used. IVDs L1/2, and L3/4 levels were injured percutaneously with a size 15 blade, under fluoroscopic guidance, to induce disc degeneration. The L2/3, L4/5, and L5/6 discs were reserved as uninjured controls. Eight weeks post-disc injury, the discs were randomly assigned to the following groups: 1) hydrogel injection (control); 2) saline injection (control); and 3) allogeneic bone marrow stromal cells suspended in hydrogel. In each case, the discs were injected with BMSC cells which were placed into the central region of the nucleus pulposus (NP). Twenty-four weeks following the injections, the goats were sacrificed and IVDs were isolated. The biochemical composition of the NP and annulus fibrosus (AF) of each disc was assessed and analyzed using the Student t-test. RESULTS: Twenty-four weeks after the injections, NP tissues transplanted with bone marrow stromal cells suspended in hydrogel accumulated 45% more proteoglycan (PG) than tissues treated with hydrogel without cells (p50.05, n57). In the AF tissues, no difference in PG accumulation was found between the discs treated with bone marrow stromal cells and the two control groups (pO0.05). CONCLUSIONS: This study is the first to explore the goat IVD as a promising large animal disc degeneration model for therapy with bone marrow stromal cells. We have shown a small but significant increase in PG accumulation by the NP tissues at 24-weeks post-treatment. Further studies with a larger sample size are indicated.
Figure. Figure.
FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
doi: 10.1016/j.spinee.2009.08.064
doi: 10.1016/j.spinee.2009.08.065
Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S-205S
similar to pre-operative and comparable to that in patients undergoing lumbar surgery at 1.5 years. Smoking, COPD, and female gender are possible factors in the development of post-operative dysphagia. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
51. Effect of a Novel Bioscaffold on DBM in an Athymic Rat Spinal Fusion Model William Lloyd, BS1, Michael Larson2, Ronald Hill3; 1Pioneer Surgical, Greenville, NC, USA; 2Ibex Preclinical Research Inc, Logan, UT, USA; 3 Greenville, NC, USA
doi: 10.1016/j.spinee.2009.08.060
BACKGROUND CONTEXT: Recent studies suggest that variable responses to DBM may result from differing levels of retained BMP’s and other factors. A previous study demonstrated that a novel bioscaffold composed of denatured collagen and a high molecular weight dextran (E-Matrix) significantly enhanced the BMP-2 effect on posterior lateral fusion in a rat model. This study was undertaken to determine the effect of E-Matrix on human DBM in posterior lateral fusion. PURPOSE: The purpose of this study was to determine whether E-Matrix improves the consistency of the response to DBM bone grafts and improves spinal fusion results. STUDY DESIGN/SETTING: Animal model (in vivo). PATIENT SAMPLE: 22 Athymic Sprague-Dawley rats. OUTCOME MEASURES: Fusion by manual palpation, radiography and histopathology. METHODS: This study compared: a commercially available human DBM bone graft; a bone graft consisting of human DBM, a novel bioscaffold carrier composed of denatured collagen and dextran (E-Matrix) and nanocrystalline hydroxyapatite granules (E-Matrix/nano DBM); and allograft in an athymic rat posterior-lateral spinal fusion model. Animals were randomly assigned to the three treatment groups: allograft (N56), commercial DBM (N58), or E-Matrix/nano DBM (N58). The test or control article was placed bilaterally (0.3 ml per side) over and between the decorticated transverse processes between the L4 and L5 vertebrae. Radiographs were taken immediately after surgery and at the 8 week termination. Bilateral fusion was assessed by manual palpation performed by 2 independent observers blinded to treatment group and by histopathology. Statistical comparisons were made using a one-way ANOVA and SNK procedure as appropriate. RESULTS: Both the commercial DBM and E-Matrix/nano DBM resulted in 100% fusion (16/16 sites, 8 animals each) by manual palpation compared to only 2/12 sites (6 animals) in the allograft control. Similar findings were noted in the radiographic analysis. However, the histological results revealed that E-Matrix/nano DBM resulted in a statistically significant increase in the percentage of new bone filling the implant site between the transverse processes compared to commercial DBM or allograft (84 6 7%, 38 6 10% and 12 6 7% respectively, mean 6 sem, p!0.05). E-Matrix/nano DBM resulted in a statistically greater tissue response score (Regenerative Degenerative Tissue Responses) compared to the other treatment groups: 8.7 6 0.6, 5.4 6 1.0, and 3.4 6 0.9 respectively (mean 6 sem, p!0.05). CONCLUSIONS: E-Matrix/nanoss DBM resulted in an improved tissue response, greater bone formation, and less variability in these responses compared to a commercially available DBM and allograft controls. This improved spinal fusion response is analogous to previously published data demonstrating fusion at lower concentrations of BMP2 when mixed with E-Matrix in a rat model. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
Wednesday, November 11, 2009 5:10–6:10 PM Focused Paper Presentations 3: Basic Science 50. Transplantation of Bone Mesenchymal Stem Cells Reduced Plasma Adrenocorticotropic Hormone Content in Rats with Spinal Cord Injury: A Potential Anti-Chronic Stress Mechanism Jun Zhou, MD, PhD1, Huilin Yang, MD, PhD1, Jie Ding, MD, PhD2, Jiannong Cen, PhD3, Zhenjiang Li, PhD3; 1The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; 2Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Jiangsu Institute of Hematology, Suzhou, Jiangsu, China BACKGROUND CONTEXT: Recent studies have demonstrated potential therapeutic effects of bone mesenchymal stem cells (BMSCs) to spinal cord injury (SCI) in rat model. However, the exact mechanism is still unknown. The authors investigated a potential anti-chronic stress mechanism of BMSCs transplantation for rat SCI. PURPOSE: To investigate a potential anti-chronic stress mechanism of transplanted BMSCs for rat SCI. STUDY DESIGN/SETTING: Experimental spinal cord injury using a rat model. PATIENT SAMPLE: No patients were enrolled in this study. OUTCOME MEASURES: N/A. METHODS: A total of 48 adult male SD rats were divided into 3 groups randomly: control, model and treatment group, n516 in every group. Rats in model and treatment group were performed a partial low thoracic SCI by modified Allen’s method at T10. Rats in ontrol group received only laminectomy. At day 7 After SCI, the dura at L4-L5 intervertebral space was exposed; 100 l of Hank’s buffered saline solution contained 1 million rat BMSCs or the same amount of Hank’s buffered saline solution was injected into the subarachnoid space. Evaluated hind limb motor function by Basso, Beattie and Bresnahan (BBB) scale pre-injection and at day 14, 28 post-injection. Half of rats in every group were anesthetized at day 14, 28 post-injection, collected blood for detection of plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT) content by enzyme linked immunosorbent assay (ELISA). RESULTS: At day 3, 7 days after surgery, BBB scale score of rats in model and treatment group was lower than control group (p!0.01). After transplantation of BMSCs, BBB scale score of rats in treatment group increased progressively, higher than those in model group at day 14, 28 post-injection, but still lower than control group (p!0.01). At day 14 post-injection, the plasma ACTH content in model group were higher than control group (p!0.05);but there was no significant difference in serum CORT content between the three groups. At day 28 post-injection, the plasma ACTH content in model group were higher than treatment group (p!0.05), and the serum CORT content in model group were higher than control group (p!0.05). CONCLUSIONS: BMSCs transplantation could improve the hindlimb motor function of SCI rats, reduce plasma ACTH content, which implied a potential anti-chronic stress mechanism of transplanted BMSCs for rat SCI. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. doi: 10.1016/j.spinee.2009.08.062
doi: 10.1016/j.spinee.2009.08.063
52. Effects of Chronic Cyclic Loading on the Lumbar Spine: An In Vivo Pilot Study Glenn Sanders1, Sarah Linley1, Daniel Ramsey1, Rosalyn Abbott1, J. Puzas2, Joseph Glennon3, Darryl DiRisio, MD4, James Lawrence4, Allen Carl, MD4, Eric Ledet, PhD5; 1Rensselaer Polytechnic Institute, Troy, NY, USA; 2Rochester, NY, USA; 3Capital District Veterinary Surgical Associates, Pattersonville, NY, USA; 4Albany Medical College, Albany, NY, USA; 5Troy, NY, USA BACKGROUND CONTEXT: Epidemiologic data indicate a correlation between cyclic axial compression and degenerative disc disease (DDD)
Proceedings of the NASS 24th Annual Meeting / The Spine Journal 9 (2009) 1S-205S in the lumbar spine. Clinically, endplate sclerosis is often observed concomitant to DDD; however, the relationship between cyclic loading, endplate sclerosis, and DDD is uncharacterized. Repeated mechanical loading may initiate subchondral sclerosis, which subsequently diminishes diffusion to and from the disc, ultimately leading to DDD. PURPOSE: The purpose of this study was to characterize the temporal effects of in vivo chronic cyclic compression on: disc height, diffusion, subchondral sclerosis, and disc morphology in the lumbar spine. STUDY DESIGN/SETTING: New Zealand white rabbits underwent loading of the lumbar spine. PATIENT SAMPLE: New Zealand white rabbits. OUTCOME MEASURES: N/A. METHODS: New Zealand white rabbits underwent a surgical procedure where pins were placed transversely through the L4 and L5 vertebrae. Four percutaneous posts, extending dorsally from the vertebrae, were attached to the pins to facilitate manipulation of the vertebrae from an external apparatus. A novel external load frame was used to apply daily cyclic axial compression to the conscious animals. Forces equivalent to 5 x BW were applied at one of two physiologically relevant frequencies. Cyclic compression was applied 2 hrs/day, 5 days/week, for 6 months. Radiographs were taken every two weeks throughout the study to assess changes in disc height and to monitor onset of sclerosis. After 6 months of loading, rabbits were administered gadolinium, euthanized and MR imaged to assess diffusion and disc morphology. MicroCT analysis was conducted to quantify changes in subchondral bone density. Morphologic changes of the disc, endplate, and subchondral bone were assessed via histology. RESULTS: Animals in the high frequency group underwent up to 2.2 million loading cycles. Plain radiographs indicated no discernable loss of disc height in both frequency groups. However, there was evidence of sclerotic changes and osteophyte formation at loaded levels. T1 and T2-weighted MR images showed no consistent pattern of signal change at loaded levels compared to the adjacent levels, however the resolution of MRI was poor for assessing the small discs. MicroCT analysis revealed a consistent increase in subchondral bone density at loaded levels compared to adjacent control levels, as shown in the Figure. CONCLUSIONS: We have developed a novel in vivo model for studying the effects of cyclic loading on the intervertebral disc, endplate, and subchondral bone. This model can be utilized to characterize the mechanism of pathology and its dependence on factors such as load magnitude, frequency, and duration. In this pilot study, our data indicate that plain radiographs and MRI – two clinically relevant diagnostic measures – did not detect early morphologic changes to the disc in response to repeated cyclic loading at physiologic magnitudes and frequencies. However, there was evidence of sclerotic changes to the subchondral bone and osteophyte formation in response to these loads. This finding is significant in that subchondral sclerosis has previously been shown to impede diffusion to and from the intervertebral disc, ultimately initiating or exacerbating disc degeneration. Our data indicate that subchondral sclerotic changes occur in response to repeated cyclic axial loading, suggesting a mechanism linking repeated mechanical loading to DDD.
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53. Transplantation of Goat Bone Marrow-Derived Stromal Cells to a Degenerative Intervertebral Disc in a Goat Disc-Injury Model Yejia Zhang, MD, PhD1, Susan Drapeau, PhD2, Howard An, MD3, Eugene Thonar, PhD3, D Greg Anderson, MD4; 1Rush University Medical Center, Chicago, IL, USA; 2Memphis, TN, USA; 3Chicago, IL, USA; 4 Rothman Institute, Philadelphia, PA, USA BACKGROUND CONTEXT: Disc injury models in small animals have disadvantages: the small disc size makes it difficult to inject adequate volumes for tissue engineering studies and the persistence of notochordal cells within the small animal discs limit their applicability as a model for human disc degeneration. The goat was selected because its intervertebral discs (IVDs) are similar in shape and in size to human discs. Bone marrow stromal cells were used because they are free of ethical concerns related to embryonic stem cells. PURPOSE: This is a pilot study to examine the effects of bone marrow stromal cells (BMSC) on degenerating IVDs in the goat. STUDY DESIGN/SETTING: This is a basic science study using a goat disc degeneration model to examine the effects of bone marrow-derived stem cells on degenerating discs. PATIENT SAMPLE: N/A. OUTCOME MEASURES: The biochemical composition of the NP. METHODS: Twenty-four goats (4 years-old) were used. IVDs L1/2, and L3/4 levels were injured percutaneously with a size 15 blade, under fluoroscopic guidance, to induce disc degeneration. The L2/3, L4/5, and L5/6 discs were reserved as uninjured controls. Eight weeks post-disc injury, the discs were randomly assigned to the following groups: 1) hydrogel injection (control); 2) saline injection (control); and 3) allogeneic bone marrow stromal cells suspended in hydrogel. In each case, the discs were injected with BMSC cells which were placed into the central region of the nucleus pulposus (NP). Twenty-four weeks following the injections, the goats were sacrificed and IVDs were isolated. The biochemical composition of the NP and annulus fibrosus (AF) of each disc was assessed and analyzed using the Student t-test. RESULTS: Twenty-four weeks after the injections, NP tissues transplanted with bone marrow stromal cells suspended in hydrogel accumulated 45% more proteoglycan (PG) than tissues treated with hydrogel without cells (p50.05, n57). In the AF tissues, no difference in PG accumulation was found between the discs treated with bone marrow stromal cells and the two control groups (pO0.05). CONCLUSIONS: This study is the first to explore the goat IVD as a promising large animal disc degeneration model for therapy with bone marrow stromal cells. We have shown a small but significant increase in PG accumulation by the NP tissues at 24-weeks post-treatment. Further studies with a larger sample size are indicated.
Figure. Figure.
FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
doi: 10.1016/j.spinee.2009.08.064
doi: 10.1016/j.spinee.2009.08.065