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Final Agenda

Final Agenda

Meeting Highlights

The History of the ICRS: The Past 20 Years
Long Term Clinical Studies
Growth Factors, PRP, Scaffolds
Chondrocytes Stem Cells & MSC’s
Advancements in Cartilage Repair & Regenerative Medicine
Perspectives for Early OA & Meniscus
The Future of the ICRS: The Next 20 Years
OA Panel Discussion
High Impact Late Breaking Abstracts

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  • 7:59 - 10:00 ICRS Patient Registry Advisory Board Meeting (Board Members only)
    Chair:
     Erggelet Christoph
    Erggelet Christoph
  • 8:00 - 10:00 Session 7: Free Paper Session: New Advancement In The Treatment Of Articular Cartilage - ICRS Generation Next Presentations: Basic & Clinical
    Moderator:
     Gomoll Andreas
    Gomoll Andreas
    Moderator:
     Papacostas Emmanuel
    Papacostas Emmanuel
    10 Min
    Clinical comparison of Matrix-encapsulated autologous chondrocyte implantation (MECI) to treat chondral defects in the knee with versus without other previous treated lesion.
    Purpose: To compare the clinical and image effect of MECI to treat knee chondral defects isolated and associated to another previous-treated lesion. Methods: Prospective cohort. Patients underwent to MECI without any other associated lesion (Only-Chondral Defect Group or OCDG) and them which lesion were diagnosed in a previous treatment of another lesion (Previous-Treated Lesion Group or PTLG). Follow-up was performed with clinical scores and T2-Mapping-MRI before surgery and 6, 12, 24, 36, 48 and 60 months post-op. Results: Fifty-two patients were included with an average age of 35±9.01 years. 20 patients included to OCDG and 32 patients included to PTLG. Average Tegner activity score of OCDG compared to PLG was 7.11±1.56 vs 7.09±1.93 before lesion (P=0.983), 3.00±2.59 vs 3.66±2.68 before surgery (P=0.420), ascending to 5.71±2.21 vs 5.00±2.45 at 60 months (P=0.887). Average Lysholm knee scoring was 57.33±21.54 vs 51.34±21.05 before surgery (P=0.343) ascending to 78.17±20.31 vs 86.33±18.33 at 60 months. CartiGram miliseconds relaxation time for native cartilage was 36.88±6.19 vs 37.41±8.74 (P=0.373) at 3 months post-op and for implant was 52.92±6.78 vs 55.41±15.55 (P=0.361). At 60 months post-op native cartilage was 40.72±6.60 vs 39.02±5.55 (P=0.550), implant was 40.02±10.07 vs 44.27±8.69 (P=0.338). Conclusion: MECI produces clinical and MRI-image improvement both as a single treatment and in conjunction with another previous treatment.
     Arredondo-Valdés Reynaldo
    Arredondo-Valdés Reynaldo
    10 Min
    Chondrogenic differentiation of whole fat tissue: A novel approach to Cartilage Regeneration
    Purpose: Despite tremendous in vitro achievements, the clinical breakthrough towards a routine application of cartilage tissue engineering is still missing. Scaffold materials available so far have not been able to produce sufficiently long lasting hyalinous cartilage. As adipose tissue contains stem cells in a collagen and glycosaminoglycan-containing matrix, the chondrogenic differentiation of total fat tissue might pose an alternative to scaffold development. Materials & Methods: Fat tissue biopsies were cultured either in chondrogenic differentiation medium or in control cell culture medium without previous isolation of stem cells. Histology, Collagen and glycosaminoglycan synthesis and mechanical strength were evaluated. Results: The chondrogenic grafts showed a smooth surface remodelling. Histology resembled the morphology of articular cartilage with positive Alcian Blue and Safranine O staining. Average glycosaminoglycan content was 16,92 µg/mg tissue versus 1,92µg/mg in the control samples (p<0,0001). Total collagen content was 8,76 µg/mm versus 0,27 µg/mm in the controls (p<0,0001), and durometrical hardness was 5 Shore versus 0,25 Shore in the controls (p<0,0001). Conclusion: Total adipose tissue can be successfully differentiated towards a tissue of a chondrogenic phenotype and shows a potential to create a fully autologous, scaffold free cartilage transplant.
    Eder Claudia
    Eder Claudia
    10 Min
    Development of scaffold-free tissue-engineered construct (TEC) with chondrogenic differentiation capacity using rabbit embryonic stem cell-derived mesenchymal stem cells
    Purpose The purpose of the present study is to develop a scaffold-free three-dimentional tissue-engineered construct (TEC) from embryonic stem cells (ESCs) and to investigate its feasibility to facilitate cartilage repair, in comparison with that of prior art TEC derived from mesenchymal stem cells (MSCs). Materials & Methods Rabbit ESC-based TEC (eTEC) was generated by hypoxic stepwise differentiation via ESC-derived MSCs (eMSCs). Quantitative PCR, glycosaminoglycan assay, and histological assessment were performed in pre- and post- chondrogenic conditions. Gene expression of eMSCs was further assessed based on microarray analysis. The rabbit synovial MSCs and TEC derived from them (sTEC) served as control. TECs combined with beta-TCP were implanted into 5 mm diameter, 6mm deep osteochondral defects created on the femoral grooves of skeletally mature rabbits, which were sacrificed at 4, 8, and 24 weeks postoperatively. Results The in vitro results demonstrate the analogy between both TECs except that eTEC has a significantly higher chondrogenic potential than sTEC. Microarray analysis showed that tumor-related genes were attenuated over time in chondrogenic differentiation of eMSCs. Implantation of the composite of eTEC leads to cartilage repair superior to that of sTEC both in quality and speed. Conclusion TEC can be an applicable local deliver system with efficacy and safety in ESC-based cell therapy for cartilage repair.
    Moriguchi Yu
    Moriguchi Yu
    10 Min
    Mechanical compression enhances cartilage matrix synthesis of the expanded osteoarthritic chondrocytes
    A study was conducted to evaluate of the biosynthesis of isolated osteoarthritic chondrocytes to varying dynamic compressive strain and loading duration. The proximal tibial was resected as a single osteochondral unit during total knee replacement surgery from patients (N=20). Scanning Electron Microscope (SEM) and atomic force microscopy (AFM) were used to measure the microstructure of cartilage interface. The isolated osteoarthritic chondrocytes were seeded with 3% agarose, subjected to 10% and 20% uniaxial dynamic compression for 4- and 8-days using bioreactor system. The deformed cellular lacunae in the osteoarthritic cartilage was detected by SEM. AFM analysis demonstrated that collagen fibrils in the extracellular matrix region of normal cartilage were denser and shorter while in osteoarthritic cartilage, they were longer and less dense. The compressed osteoarthritic chondrocytes showed more intense and broader deposition of collagen type VI compared to control. The expression of collagen type VI was directly proportional to the duration of compression in which 8 days compression was significantly higher than 4 days compression. The 20% compression showed significantly higher intensity compared to 10% compression in 4- and 8-days. It is apparent that the biosynthetic activity of human chondrocytes from osteoarthritic joints can be enhanced using selected compression regimes.
     Chong Pan Pan
    Chong Pan Pan
    10 Min
    Effects of Micronized Cartilage Matrix on Cartilage Repair in Osteochondral Lesions of the Talus
    INTRODUCTION: A promising technique for treatment of osteochondral lesions of the talus (OLT) uses an acellular micronized cartilage matrix (MCM), BioCartilageâ to fill the lesion. Marrow cells from microfracture are thought to repopulate MCM and form hyaline-like cartilage. The effect of MCM on bone marrow cells remains untested. We hypothesized that adding bone-marrow derived stem cells to MCM would result in chondrogenic differentiation. Verifying combination of matrix and cells resulting in cartilage regeneration would affirm a reliable, one-step treatment of OLTs. METHODS: Human bone marrow-derived stem cells were expanded in monolayer culture. Stem cells were mixed with MCM at the manufacturer recommended ratio for reconstitution. 2x106 Cells were well-cultured with MCM in chondrogenic media. Cell viability, gene expression, and histology were performed after 3 weeks. RESULTS: Rehydrating MCM prior to addition of cells was required for cell viability. The combination of stem cells and MCM produced a cohesive structure, with 98% cell viability. Stem cells alone did not form viable constructs. DISCUSSION: MCM is a suitable scaffold for the chondrogenic differentiation of bone marrow-derived stem cells, given that the matrix is first rehydrated before adding cells. Preliminary results suggest cartilage matrix deposition occurred surrounding the cells after 3 weeks of chondrogenic culture.
     Lee Cassandra
    Lee Cassandra
    10 Min
    Articular Cartilage Repair with Mesenchymal Stem Cells following Chondrogenic Priming in Normoxic and Hypoxic Conditions: A Preclinical Pilot Study
    Purpose This study assessed a novel protocol that involved transplantation of bone marrow mesenchymal stem cells (BMSCs) into articular cartilage defects in sheep following a short period of chondrogenic priming. The impact of oxygen tension during pre-implantation culture was also investigated. Methods Ovine BMSCs were isolated, expanded, seeded within a hyaluronic acid scaffold, primed ex vivo in chondrogenic medium for 4 days under normoxia (21% oxygen) or hypoxia (3% oxygen), and implanted within full-thickness cartilage defects in the femoral condyles of 5 sheep. Pre-implantation priming was evaluated using RT-qPCR. Six months after implantation, histological assessment was performed on tissues. Results Priming of pre-implantation BMSCs resulted in increased expressions of collagen II and aggrecan in comparison to unprimed BMSCs (p<0.05). BMSC-seeded scaffolds produced proteoglycan-rich cartilaginous tissues. Defects implanted with BMSC-seeded scaffolds had larger repair tissue areas, percentages of defect fill and O’Driscoll histological scores than cell-free controls (p<0.05). A difference in histological scores was not found between tissues derived from hypoxia- and normoxia-cultured BMSC-seeded scaffolds (p=0.90). Conclusion We demonstrate that priming for a short period (4 days) improves the chondrogenic gene expression profile of BMSCs, chondrogenically primed BMSCs produce superior cartilaginous tissue to cell-free controls, and oxygen tension during pre-implantation culture does not consistently modulate repair tissue formation in this model.
     Bornes Troy
    Bornes Troy
    10 Min
    Peptidomic Analysis of Cartilage and Subchondral bone from OA patients
    Purpose: In patients with cartilage lesions and osteoarthritis, pain is one of the major reasons for seeking medical care, yet the knowledge on the pain origin is very limited. Studies suggest pain is affected both by mechanisms involving neuropeptide signaling, peripheral and central sensitization but also psychological factors altering the pain perception. The purpose of this study was to develop a method for directly analyzing bone samples and enablingidentification of peptides that may play a role in pain development. Materials and Methods: Femur condyle bone samples from zones with manifest cartilage damage and macroscopically healthy zones were collected from 6 patients undergoing total knee arthroplasty. The samples were demineralized, marked with Tandem Mass Tag labeling and analyzed using liquid chromatography coupled with tandem mass spectrometry. Results: Using peptidomics, 6,292 endogenous peptides were identified. 248 peptides differed significantly from damaged zones compared to macroscopically healthy zones. None of the neuropeptides identified differed significantly. However the findings of SHANK2 and TENASCIN-R were interesting with their special connections to chronic pain and neuron protections. Conclusions This pilot study shows promising results for the usage of peptidomics to identify endogenous peptides that may play a role in the pain mechanisms involved in OA.
     Gatenholm Birgitta
    Gatenholm Birgitta
    10 Min
    Four Years Follow-up of Arthroscopic Meniscal Allograft Trasplantation: the chondroprotective effect evaluated by T2-Mapping
    Purpose: to evaluate quantitatively by T2-mapping the chondroprotective effect of MAT at 4-years follow-up. Material & Methods: Twenty-one patients with medial post-meniscectomy syndrome with ages 18 to 50 years. Fresh frozen (FF) and gamma irradiated (GI) grafts were used. All MAT were performed arthroscopically. Clinical evaluation was performed pre-op and at 12, 24, & 48 post-op. T2-mapping to evaluate the chondroprotective effect was done. Results: A total of 21 patients were included with 22 MAT procedures (12 FF & 10 GI); mean age 31 years. Clinical scores improved significantly from pre-op to 4 years follow-up: IKDC (0.001), Lysholm (0.001), Tegner (0.001); KOOS: symptoms (0.001), pain (0.002), sports (0.001), & Quality of life (0.001). T2-mapping evaluation in femur and tibia at pre-op (35.41, 36.55) compared to 12m (37.17, p=0.110 & 34.33, p=0.488) and 24m (38.47, p=0-098 & 38.47, p=0-169) were not significant different; pre-op values compared to 36m (39.95, p=0.002 & 41.35, p=0.013) and 48m (40.33, p=0.003 & 41.49, p=0.003) had significant increase. Conclusions: Although T2-mapping values showed significant increase after 4 years of meniscal allograft transplantation those values can not be considered as cartilage degenerative changes due to are still into the range of healthy cartilage.
     Olivos Meza Anell
    Olivos Meza Anell
    10 Min
    Metabonomic profiling of early and late stage knee osteoarthritis synovial fluid
    Purpose: The purpose of this study was to use Nuclear Magnetic Resonance (NMR) spectroscopy to generate multiparametric metabolite concentration profiles of knee joint synovial fluid from chondral lesion and severe osteoarthritic (OA) patients, ultimately to identify diagnostic and prognostic metabolic biomarkers of lesion progression. Materials & Methods: Joint fluid was aspirated from 9 patients with focal cartilage lesions (ICRS grade II/III), and 9 patients with severe OA (KL grade III/IV). 1H 500MHz NMR spectroscopy was performed and relative intensities of spectral signals of glutamate, glutamine, creatine, glucose, alanine, lactate, phenylalanine, leucine, isoleucine, citrate, and valine were compared. Students t-tests and principle least squares discriminant analysis was used to identify strongest discriminatory metabolites between cohorts. Results: T-tests revealed there was significantly higher (p<0.05) levels of glutamate in severe OA fluids compared to chondral lesion fluids. Discriminant analysis revealed the strongest significant (p<0.05) discriminators between groups were glutamate, citrate and creatine. Conclusions: These results suggest glutamate, a neurotransmitter responsible for joint pain and inflammation, is the strongest candidate for a metabolic biomarker of joint lesion progression to OA. Changes in citrate and creatine levels may be due to energy dysregulation of joint tissues, and they could potentially be candidates if investigated further.
    Khatib Nidal
    Khatib Nidal
  • 10:00 - 10:30 Coffee Break / Intermission / Exhibition
  • 10:30 - 11:15 Session 8: Panel Discussion - The Disease Continuum: When is a Focal Defect OA and Is OA a Curable Disease?

    Panellists: Tom Minas,  Christian Lattermann, Anders Lindahl, Lars Petersen, Nori Nakamura, Bill Bugbee, George Bentley, Anthony Hollander

    Moderator:
     Brittberg Mats
    Brittberg Mats
    Moderator:
     Zaslav Kenneth
    Zaslav Kenneth
    Panellist:
     Minas Tom
    Minas Tom
    Panellist:
     Bugbee William
    Bugbee William
    Panellist:
     Lattermann Christian
    Lattermann Christian
    Panellist:
     Grande Daniel
    Grande Daniel
    Panellist:
     Lindahl Anders
    Lindahl Anders
    Panellist:
     Peterson Lars
    Peterson Lars
    Panellist:
     Nakamura Norimasa
    Nakamura Norimasa
    Panellist:
     Hollander Anthony
    Hollander Anthony
    Panellist:
     Bentley George
    Bentley George
    15 Min
    Is it Time for Joint Preservation/Cartilage Repair Surgery to have a Place in Traditional OA Treatment Algorithm?
     Bugbee William
    Bugbee William
  • 11:30 - 12:30 Session 9: The Next 20 Years... Discussion on the Future of our Society & Regenerative Medicine

    Chair: Ken Zaslav – Panelists: Alberto Gobbi, Elizaveta Kon, Tom Minas, Dan Grande, Jos Malda 

    Box lunches and drinks will be available during the discussions  

    Chair:
     Zaslav Kenneth
    Zaslav Kenneth
    Panellist:
     Gobbi Alberto
    Gobbi Alberto
    Panellist:
     Kon Elizaveta
    Kon Elizaveta
    Panellist:
     Minas Tom
    Minas Tom
    Panellist:
     Grande Daniel
    Grande Daniel
    Panellist:
     Malda Jos
    Malda Jos
  • 13:00 Official Summit Adjourn
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