2nd Annual TISSUE AND GENETIC ENGINEERING for the Treatment of Arthritic Diseases

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Overview

The 2nd annual Tissue Engineering conference will take place as scheduled.

Our deepest sympathy's go out to the people involved in the widespread tragedy of Tuesday, September 11, 2001. There are no words to describe the senselessness of this horrible act. Our thoughts are with the families at this time.

Sincerely,
Craig Wohlers
President

Agenda updated on October 2nd

Finding suitable biomaterials for hard tissue replacement and new approaches for tissue regeneration are major aspects of orthopedic research for arthritic diseases. The combination of material engineering with life sciences and genetic engineering leads to novel therapeutic strategies and new approaches for the development of biological substitutes in order to restore and improve tissue functions.

This conference will showcase the most recent advances in chondrocyte transplantation, proliferation and cartilage engineering as well as their impact on the immune system. In addition, in depth coverage on gene therapeutic strategies in arthritis will be presented.

* Articular Cartilage Crafts
* Strategies in Cell-Based Technologies to Attain Tissue Specificity
* Biomimetic Surfaces and Cell Adhesion
* Mechanical Forces
* Scaffolds in Cartilage Tissue Engineering
* Measuring Cartilage Stiffness
* Immunological Approaches to Stabilize and Protect Engineered Cartilage Transplants
* Immune Responses to Allogeineic Mesenchymal Stem Cells
* Direct Gene Delivery
* Gene Transfer in Rheumatoid Arthritis

This unique conference brings together experts from industry and academia to bridge the gap between material science and cell biology to improve the treatment for arthritic diseases. Take advantage of this special designed meeting and register early to reserve your place!

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Agenda

Thursday, October 4, 2001

9:30 Chairperson's Opening Remarks
Michael Sittinger, Associate Professor, Laboratory for Experimental Rheumatology and Tissue Engineering, Medical Faculty Charite Berlin, Germany

CELL TRANSPLANTATION

9:35 Strategies in Cell-Based Technologies- Cell Orientation Guided in Design by Scaffold vs. Cell-Cell Interaction and Matrix Production Directing Tissue Fabrication
Timothey Ganey, Ph.D., Co.don Tissue Engineering, Inc.
Cell-based technologies offer the opportunity to direct phenotypic identity for specific and localized treatment. Although all tissues optimize a structure that reduces strain, individual morphology of the tissues reflects different strategies to attain this condition. Chondrocytes, osteoblasts, disc chondrocytes, and endothelial cells have been successfully used in cell-based repairs. Chondrocytes respond to variations in dynamic forces to optimize a matrix that neutralizes strain, in essence structuring water by electrochemical interaction to dissipate compressive forces of loading. The matrix-rich adult morphology emerges from a highly cellular embryonic and immature morphotype that is modeled to individual loading demands.
Separately, cell-based treatments such as endothelialized heart valves require a morpholog from the outset of implantation that carries functional capacity. Based on the immediate needs, a hybrid strategy offers an option where endothelial cells on a biodegradable scaffold can provide a functional, yet biologic solution to a medical problem.
While optimal cell environment is directed at a common final goal, the course in attaining tissue specificity must take into account progressive changes that accent the functional development.

10:10 Articular Cartilage Grafts
Barbara Huibregtse, Senior Scientist, Genzyme
This talk will cover development of a second generation product of Carticel TM (Autologous Chondrocyte Implantation).

10:45 Mesenchymal Stem Cell Therapy in Joint Disease
Frank Barry, Director, Arthritis Research, Osiris Therapeutics Inc.
Mesenchymal stem cells (MSCs) isolated from bone marrow have the capacity to differentiate into several mesenchymal tissues, including bone, cartilage and adipose tissue. Data will be presented showing that delivery of cells to joints with meniscal injury inhibits progressive changes associated with osteoarthritis and therapeutic strategies in joint disease will be discussed.

11:20 Refreshment Break and Poster/Exhibit Viewing

CELL PROLIFERATION AND ADHESION

11:50 Optimizing Tissue Engineering for Cartilage
Barbara D. Boyan, Professor and Director of Orthopedic Research, University of Texas Health Sciences Center at San Antonio
Development of cartilage replacement, repair, and regeneration materials is confounded by the need for long-term animal studies to ensure even incremental improvement over current therapy. We have developed pre-screening strategies to limit the size and scope of large animal trials. One concern has been the differences in phenotypic expression of chondrocytes in vitro and in vivo. Data will be presented showing an analysis of chondrocyte response to growth factors and scaffold design in vitro and in a nude mouse model. Results will be compared to the behavior of the scaffold in a large animal goat model.

12:25 Biomimetic surfaces to control cell adhesion and promote bone formation in vitro
Andrés J. García, Ph.D., Assistant Professor, Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
Cell adhesion to extracellular matrices through integrin receptors anchors cells and triggers signals that direct cell proliferation and differentiation. We are pursuing two biomolecular strategies for engineering surfaces to control integrin binding in order to direct bone cell function and in vitro matrix mineralization. These approaches provide a basis to the rational design of robust biospecific surfaces that tailor adhesive interactions and elicit specific cellular responses.

1:00 Luncheon, Hosted by The Knowledge Foundation

SCAFFOLDS AND BIOMECHANICS

2:30 Cartilage Tissue Engineering and the Role of Mechanical Forces
Alan J. Grodzinsky, Director, MIT Center for Biomedical Engineering, Professor of Electrical, Mechanical and Bio-Engineering, MIT
Certain amino acid sequences of alternating hydrophobic and hydrophilic side groups form beta sheets in water that subsequently self-assemble into a stable gel in electrolyte solutions. Such peptide gels may have significant advantages for cartilage tissue engineering. Chondrocyte encapsulation, culture, and the time evolution of matrix deposition and biomechanical properties are desribed. The potential role of mechanical forces in cell-construct optimization is discussed.

3:05 Scaffolds for Cartilage Tissue Engineering
Jens Riesle, PhD, Senior Research Scientist, IsoTis NV, Bilthoven, The Netherlands
Our approach adopts a porous polymer scaffold with similar mechanical properties to native articular cartilage, which acts as a 3D carrier for seeding autologous chondrocytes and subsequent in vitro tissue culture. The presentation will cover 1) mechanical and protein release properties of various scaffolds and 2) cartilaginous tissue formation within the 3D carrier.

3:40 Refreshment Break

4:00 An Instrument for Measuring Cartilage Stiffness
Gabriele G. Niederauer, Ph.D., Director of Research and Development, OsteoBiologics, Inc.
OVERVIEW: The in vivo assessment of the quality of cartilage is a critical tool to determine how to clinically treat damaged cartilage. Utilizing non-destructive indentation, a hand-held instrument (ACTAEON(tm) Probe) can be used to rapidly measure the stiffness of articular cartilage, which can then be correlated to cartilage condition. This information can be of significant value to the clinician in detecting degenerative cartilage in human joints.
PRESENTATION TOPICS:
* Use of rapid indentation to measure the stiffness of cartilage
* Correlation of ACTAEON(tm) Probe stiffness measurements to other methods of characterizing cartilage
* Clinical testing of the device and its relationship to qualitative grading

4:35 Preliminary Evaluation of Injectable Cartilage Matrix
Dale P. DeVore, Chief Scientific Officer, Collagenesis, Inc.

5:15 End of Day One

Friday, October 5, 2001

8:30 Coffee and Pastries, Exhibit/Poster Viewing

9:30 Chairperson's Opening Remarks
Timothey Ganey, Ph.D., Co.don Tissue Engineering

IMMUNE RESPONSES

9:35 Immunological Approaches to in vivo Stabilization and Protection of Engineered Cartilage Transplants
Michael Sittinger, Associate Professor, Laboratory for Experimental Rheumatology and Tissue Engineering, Medical Faculty Charite Berlin, Germany
Following after in vitro studies on differentiation and extracellular matrix formation of engineered cartilage, different in vivo models contribute substantial insights leading to innovative clinical tissue engineering applications. Maintenance of tissue dimensions as well behavior and degradation of different components are frequently first evaluated in the nude mouse model. More advanced studies in immuno-competent animal models usually require entirely autologous procedures. Besides autologous cells, for long-term survival and stability of tissue engineered cartilage also other conditions such as scaffolds, cell embedding components or the maturity of engineered tissues appear to influence immunological reactions affecting the transplant. Thus, additional immunological approaches are suggested to stabilize or protect cartilage transplants in vivo. Such procedures may significantly expand clinical indications for cartilage tissue engineering in the future.

10:15 Immune Responses to Allogeneic Mesenchymal Stem Cells
Kevin R. McIntosh, Assistant Director of Immunology, Osiris Therapeutics, Inc.
Mesenchymal Stem Cells (MSCs) are rare cells found primarily in bone marrow that can be expanded in tissue culture. These cells have the capacity to differentiate into a variety of tissue types including bone, cartilage, tendon, fat, and muscle. The exploitation of these cells for tissue repair would be most easily accomplished using MSCs derived from a "universal donor". We have investigated immunological responses to allogeneic MSCs and found that MSCs do not induce proliferation of allogeneic T cells in vitro. Lack of response can be attributed to low inherent immunogenicity of MSCs and the suppressive activity that these cells exhibit for alloreactive T cell responses. These results suggest that MSCs would not be rejected after transplantation to allogeneic recipients. Recent results in a variety of animal models have verified the accuracy of this prediction.

GENE THERAPY

10:50 Molecular and cellular basis of rheumatoid joint destruction - gene transfer to identify novel therapeutic strategies
Ulf Mueller-Ladner, M.D., Department of Internal Medicine I, University of Regensburg, Germany
In rheumatoid arthritis, synovial cells are activated, attach to cartilage and bone, release several sets of matrix-degrading proteinases (MMPs and MT-MMPs), cysteine proteinases (cathepsins B, L and K) as well as serine proteinases to invade the articular structures. To identify the most relevant factors mediating joint destruction we use the SCID mouse model and ex vivo gene transfer of protective genes, anti-sense sequences and ribozymes.

11:25 Refreshment Break and Poster/ Exhibit Viewing

12:00 Gene Therapy for Canine Osteoarthritis: A Novel Dual Promoter Targeting System
Sarah E. Campbell, Molecular Therapeutics Research Group, Department of Clinical Studies, Faculty of Veterinary Medicine, University of Glasgow, UK

12:35 Combined Tissue Engineering/ Gene Therapy Strategies for Repair of the Musculoskeletal System
Daniel Grande, Director, Orthopaedic Research Laboratory, Dept. of Orthopaedic Surgery, North Shore/ LI Jewish Health System, Manhasset NY
The successful repair of damaged articular and meniscal cartilage remains one of the most difficult challenges in orthopaedic surgery. In vitro cultured tissue constructs have been assembled which can deliver cells transduced with genes important in directing chondrogenesis during development. We will demonstrate the results using this strategy in healing articular cartilage and meniscal defects.

1:15 End of Conference

Call for Posters

Industry and academic scientists are encouraged to submit poster titles for this event. One-page abstracts (8 1/2” x 11” with 1-inch margins) must be submitted no later than September 1st, 2001 for inclusion in conference documentation. Additional poster submissions will be accepted until September 24, 2001 but may not be included in conference documentation.
Note: If you are submitting a poster, you MUST be registered and paid in advance to ensure that a posterboard is reserved for you.

Sponsorship & Exhibit Opportunities
Take advantage of tailored opportunities to reach a very targeted, decision-making audience. We offer a variety of packages, each designed to maximize your organization's exposure and facilitate networking at this event. Don't miss this opportunity to showcase your products to a large audience of attendees qualified to make purchasing decision as well as demonstrate your company's position as a leader in this market.

Conference Sponsorships
A variety of conference sponsorships are available which offer incremental levels of visibility to conference delegates at the event - as well as opportunities for marketing exposure prior to the event. Taking advantage of pre-conference options has the added benefit of getting your organization's name out to a large group of interested decision makers.

Networking Event Sponsorships
These "mini" sponsorships offer representatives of your organization a dedicated opportunity to network with conference delegates - with your organization clearly recognized as the host of the event.

• Cocktail Receptions
• Luncheons
• Dinner Banquets
• Hospitality Suites

Workshop Sponsorships
Your company may sponsor an instructional workshop (subject to approval) for delegates in conjunction with the conference. Highlight your organization's expertise! Delegate feedback indicates that these scientific/technical vehicles enhance retention of your organization's presence in their minds - increasing the potential for drawing customers long after the conference is over.

Call Alan Abend at (617) 232-7400 ext. 202 or email today ( aabend@knowledgefoundation.com ) for pricing information and customization options.

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