Development of an in vitro
arthritic joint model

Alexandra Damerau
Prof. Frank Buttgereit`s group
Glucocorticoids, Bioenergetics & 3R
Department for Rheumatology andClinical Immunology
UNIVERSITÄTSMEDIZIN BERLIN

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Motivation from Clinical Perspective
Rheumatoid Arthritis (RA): 100 different forms of arthritis
 RA-Prevalence: 0.5 – 1.0% worldwide
 Patients are normally aged > 50 years; mainly women Chronic inflammatory autoimmune disease related to joints
 Functional limitation: morning stiffness, pain, immobility
 Therapeutic strategy complex with focus on remission
 no healing and medication with adverse effects

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Pathogenesis of RA
 Autoimmune disease with unknown cause Inflammation originates in the synovium
Healthy JointInduction

RARelease of inflammatory
mediators & cytokines

Chronic inflammation of thesynovial tissue
Proliferation forming„Pannus“

Cartilage and boneerosion

Joint destruction
Smolen, J.S. & Steiner, G. (2003) Nature Reviews Drug Discovery.
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Clinical Challenges in RA
Proportion of RA patients by disease activity according to DAS28-criteria1

No low diseaseactivity orremission isachieved in 26.6%of patients.

DAS = Disease Activity Score; RA = Rheumatoide Arthritis
1Haugeberg, G. et al. (2015) Arthritis Res Ther.

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There hasn`t been a complete therapy
for this disease yet.
→ basic and translational research is needed!
4Motivation from Animal Perspective

Dietzel, H.J. (2004) Trends Mol. Med.

Classification of Severity:
Moderate/Severe“… we are not 70 kg rats."
Thomas Hartung, Professor of Johns Hopkins University

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Alternatives and Limitations
In vitro models: Monolayer cultivation
 3D cultivation
 Ex vivo cultivation of patient-derived material BUT: mostly cell lines are used

Ibold, Y. et al. (2007) J. Biomol. Screen.
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Pretzel, D. et al. (2009) Arthritis
Research & Therapy.

Lozito, T. P. et al. (2013) StemCell Research & Therapy.
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Aim of the Project

Development of an in vitro 3D human disease model with thecombination of different cell systems in order to replace animal models.

Synovial Membrane
Synovial Fluid
Cartilage &Chondrocytes

Characterization& Differentation

hMSC

Subchondral Bone &Osteoblasts/-cytes

Bone Marrow & MSC

Healthy Joint

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7Aim of the Project

Development of an in vitro 3D human disease model with thecombination of different cell systems in order to replace animal models.

Hyperthrophy &Inflammation
Immune Cell
Migration &Cytokines

Application of Isolated
Immune Cells

Application hMSC
ofCytokines: TNFα, IL-6,
MIF

Cartilage &Subchondral Bone
Destruction

Inflamed Joint

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Research on Joint Disorders In Vitro

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9Expression fold change
normalized to EF1A and MSC

Expression fold change
normalized to EF1A and MSC

100000
10000
1000
100
1010.1Col1a1Col2a1

Col10

UNIVERSITÄTSMEDIZIN BERLIN10001001010.1
RUNX2 SPP1 COL1A1 ON

10Acknowledgment

Thank You for Your Attention!
Group Leader
Prof. Dr. med. Frank Buttgereit
Scientists:
Dr. rer. nat. Timo Gaber(Scientific laboratory head)Dr. rer. nat. Cindy Strehl(Administrative laboratory head)Dr. med. vet. Annemarie Lang
Manuela Jakstadt, MTA

Member ofCharité3R

PhD-Students:
Moritz Pfeiffenberger, MSc.
Alexandra Damerau, MSc

Many Thanks to our Funders

Scientist:
Dr. Igor Ponomarev

UNIVERSITÄTSMEDIZIN BERLIN

031L0070A

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