Disc and Cartilage Biology
Developing and testing of repair methods, regenerative treatments and diagnostic tools
Dr Sibylle Grad, PD
Deputy Program Leader
Focus Area Leader:
Disc and Cartilage Biology
Traumatic and degenerative damage to the articular joint and intervertebral disc (IVD) are major causes of acute and chronic pain. However, the factors that contribute to the loss of function and the underlying pathophysiology are still poorly understood. In addition, present medical and surgical approaches do not address the underlying pathology and are often unsatisfactory. We investigate potential mechanisms leading to cartilage and IVD damage and identify tissue and systemic biomarkers of degeneration, which may serve as diagnostic and therapeutic targets; we then evaluate novel biological treatments for repair and regeneration.
We have established a whole IVD organ culture system with the ability to maintain entire discs alive for several weeks under controlled nutrient and mechanical loading conditions. Within this IVD-specific bioreactor, we are investigating the beneficial or detrimental effects of nutrition, mechanical load, and/or biochemical factors on disc cell viability and metabolic activity.
Our ex-vivo IVD defect and degeneration models allow us to design and evaluate appropriate biological treatment strategies, including implantation/ homing of stem cells, delivery of anabolic, anti-catabolic or anti-inflammatory molecules, new biomaterials or combinations thereof. Data from ex vivo models are correlated to in vivo observations and clinical data to identify molecular markers of dysfunction. The goal is to develop functional therapies which, depending on the type of damage, will maintain or restore the mechanical properties of the disc, while cellular components will enhance the endogenous regenerative process.
To study the potential of new therapies for articular cartilage repair and regeneration, we have developed cartilage-specific bioreactor system applying multiaxial load to tissue-engineered constructs or osteochondral explants. The bioreactor mimics the load and motion characteristics of an articulating joint. Chondral and osteochondral defect and disease models enable us to test tailored treatments under physiologically relevant, mechanically loaded ex-vivo conditions. Cell- and material-based therapies as well as chondrogenic and anti-inflammatory factors are under investigation for cartilage repair and preservation.
Mesenchymal stem cell homing in the degenerative intervertebral disc: Characterization of disc and stem cell interactions
The aims of this project are to identify factors released by mesenchymal stem cells (MSCs) that can protect or regenerate the intervertebral disc (IVD), to demonstrate the effect of MSCs after migration into IVD tissue, and to elucidate mechanisms of MSCs migratory and stimulatory activity in the IVD.
Anti-inflammatory therapy for cartilage preservation
This project aims to establish a bioreactor loaded cartilage explant model implementing inflammatory components, and to test the anti-inflammatory and regenerative potential of small molecule delivery ex vivo.
Horizon 2020 Project (H2020-SC1-BHC)
Induced pluripotent stem cell-based therapy for spinal regeneration (iPSpine)
The aim of the iPSpine consortium is to investigate and develop a new advanced therapy medicinal product of the future, based on a novel developmental biology-based therapeutic strategy employing pluripotent stem cells (iPSC) and smart biomaterials. Read more...
In-joint application of non-viral mRNA therapy for osteoarthritis (Joint-Approach)
The Joint-Approach consortium aims to develop a novel safe non-viral and effective gene therapy-like mRNA therapy for osteoarthritis. Unique in-joint injectable polymer-based nanoparticle carriers will be used for intracellular delivery of mRNA into joint-related tissues. Read more...