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Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 271 - 271
1 May 2009
Franceschi F Longo U Ruzzini L Rizzello G Marinozzi A Denaro V
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Aims: The aim of this study was to analyze the morphological features of the human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears and glenohumeral instability.

Methods: 41 subjects were recruited for the study. 20 subjects (group 1) sustained a rotator cuff tear and proceeded arthroscopic repair of the lesion. 21 subjects (group 2) underwent surgery due to glenohumeral instability. During surgery, under arthroscopic control, a full thickness supraspinatus tendon biopsy was harvested in the middle portion of the tendon. All slices were processed for histological analysis

Results: On surgical specimens of supraspinatus tendon from patients with rotator cuff tears, but not from patients with instability, we found increased preponderance of hyaline degeneration, fibrocartilaginous or chondroid metaplasia, calcification, lipoid degeneration, mucoid or myxoid.

Degenerative changes were more evident on the articular side of the rotator cuff.

Conclusions: The present study provides a description of the histological architecture of human surgical specimens of normal supraspinatus tendon from patients with rotator cuff tears. Preexisting degenerative change in the supraspinatus tendon seems to be the main cause of rotator cuff tears.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 272 - 272
1 May 2009
Denaro V VadalĂ  G Kang J
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Aims: Recent advances in our understanding of intervertebral disc biology have led to develop novel treatments for intervertebral disc degeneration (IDD). With the ability to provide sustained delivery of a potentially therapeutic agent, gene therapy has shown much promise in regard to the treatment of IDD. The aims of this study are (part 1) to test efficacy in delaying course of IDD by intrediscal injection of adenoviral vectors carrying human BMP-2 and (part 2) to describe the application of an inducible system in order to modulate transgene expression.

Methods: (Part 1) IDD was induced in 13 NZW rabbits by anterolateral stab. Three weeks post-stab, saline with or without virus was injected directly into stabbed lumbar discs. Group 1 (n=8) received Ad/hBMP-2 while group 2 (n=5) received saline only. Rabbits were followed longitudinally with MRIs and X-rays preoperatively for up to 12 weeks post-stab. ELISAs were done to confirm BMP-2 production. (Part 2) Human nucleus pulposus cells (NPC) were transduced with an adenoviral vector that expresses GFP under the control of a tetracycline (Ad/GFPtet). Cells were cultutred with and without tetracycline. Transgene expression was assessed by detecting GFP signal with both the FACS and the fluorescent microscope.

Results: (Part 1) By 12 weeks, the saline-injected discs had lost 49% of their MRI Index, in contrast to only a 25% decrease for the Ad/hBMP-2 treated discs. X-rays demonstrated no obvious bony intervertebral fusion in either group. ELISAs confirmed vigorous hBMP-2 production 3 weeks after therapeutic gene transfer. (Part 2) NPC expressed GFP after transduction. GFP positivity was not observed two days after administration of tetracycline. The cells expressed GFP again three days after removal of tetracycline.

Discussion: The results of this study demonstrate the efficacy of vector-mediated BMP-2 gene transfer to alter the course of IDD in a reproducible animal model, as well as the potential to control transgene expression, improving safety.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 275 - 275
1 May 2009
Franceschi F Longo U Ruzzini L Rizzello G Marinozzi A Denaro V
Full Access

Aims: We reviewed our experience to determine the results of arthroscopic repair in patients over 50 with rotator cuff tears and Type II SLAP lesion in whom the repair was effected repairing the two lesions, or repairing the rotator cuff tears and performing a tenotomy of the long head of the biceps.

Methods: We recruited 121 patients older than 50 years in whom a symptomatic rotator cuff tear had failed non-surgical management and was affecting daily activities.

We assigned them retrospectively to one of the two groups: Group 1 underwent arthroscopic repair of the rotator cuff and repair of the type II SLAP lesion. Group 2 underwent arthoscopic repair of the rotator cuff tear and a tenotomy of the long head of the biceps.

Results: There was statistically significant difference in total postoperative UCLA scores and ROM when comparing the two groups postoperatively (P< 0.05).

Conclusions: We compared the clinical outcome of patients over 50 affected by the association of rotator cuff tears and Type II SLAP lesion, in whom both the defects were repaired, or the rotator cuff tear was repaired and the long head of the biceps tendon was tenotomized. In our hands, the association of rotator cuff repair and biceps tenotomy provides better clinical outcome compared with the association of Type II SLAP lesion repair and rotator cuff repair at three years of follow-up.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 152 - 152
1 Mar 2006
Denaro V Vadala G Sobajima S Kang J Gilbertson L
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Introduction: Current therapies for degenerative disc disease (DDD) are aimed at treating the pathologic and disabling conditions arising from DDD rather than directly treating the underlying problem of disc degeneration. Our group are exploring the potential of Cell Therapy to repopulate the disc and stopping the progressive loss of proteoglycans. Stem cells appear to be excellent candidates for this purpose, based on their ability to differentiate along multiple connective tissue lineages. The purpose of this study is to investigate the in-vitro interaction between muscle-deroved stem cells (MdSC) and nucleus polposus cells (NPCs) and to determine in-vivo viability of mesenchymal stem cell (MSC) in the harsh environment of the IVD

Materials and Methods: (1) Human NPCs were isolated from patients undergoing disc surgery and were co-cultured for 2 weeks with MdSCs from 3-wk-old mdx mice and in monolayer culture system at different ratios of 0:100, 25:75, 50:50, 75:25, 100:0. Proteoglycan synthesis and DNA content were measured. (2) Rabbit mesenchymal stem cells were isolated from bone marrow and tagged with a retrovirus delivered LacZ reporter gene for tracking. MSCs were then injected into a healthy rabbit IVD via 30G needle. Rabbits were sacrificed at postoperatively at 3, 6, 12 and 24 weeks. Histological analysis for MSC viability was performed.

Results: (1) Co-culturing of NPCs with MdSCs in the monolayer culture system resulted in vigorous increases in proteoglycans synthesis as compared with NPCs alone. The increases were on the 200% for an NPC-to-MDSC ratio of 75:25. DNA content also increased with co-culture. (2) Histological examination revealed presence of MSCs expressing LacZ without apparent decrease in numbers or diminishment of protein production.

Conclusion: The data from this study show that there is a synergistic effect between stem cells and nucleus pulposus cells resulting in upregulated proteoglycan synthesis in-vitro. Mesenchymal stem cells remain viable and continue to express an ex vivo transduced protein without appreciable cell loss for up to 24 weeks post transplantation into the rabbit IVD. These results suggest that MSCs can survive in the harsh environment of the IVD and may favourably modify ECM production. These studies support the feasibility of developing a stem cell therapy approach for DDD.