Funding tool: Basic research projects
Project-ID: LS11-007
Project start: 05. November 2012
Project end: will follow
Runtime: 36 months / finished
Funding amount: € 294.000,00

Brief summary:

Osteoarthritis is the most common disabling condition of humans in the western world. Additionally, its incidence is increasing with age. Overweight and sport associated overloading are the most prominent risk factors for initiation and progression of the disease. Damage of articular cartilage frequently leads to osteoarthritis due to the aneural and avascular nature of articular cartilage which impairs regeneration and repair. Therefore, we propose that patients affected by osteoarthritis will benefit from a cell-based transplantation approach. It is the aim of this proposal to use amniotic fluid-derived stem cells (AFS cells) as well as adult donor-derived chondrocytes as source material for chondrogenic differentiation. The identification and characterization of the optimal suited cell system and differentiation protocol will be a crucial goal of this project.
AFS cells are a promising new tool for regenerative medicine since they can be biobanked, proliferate extensively and show multipotent differentiation characteristics. Preliminary results pin point to a prominent role of mTOR (mechanistic target of rapamycin) in the chondrogenic differentiation process. Since mTOR signalling is the main regulator of cell metabolism and differentiation we will assess the role of mTor during in vitro cell differentiation and we will test for conditions to prevent chondrocyte hypertrophy. Likewise these conditions can also be used to improve the quality of patient-isolated passaged chondrocytes. In parallel we will also analyse patient samples affected by osteoarthritis and correlate mTor activity with progression and staging of the disease. Finally, successful chondrocyte differentiation will be functionally assessed by transplantation in a human articular cartilage explant system. It is highly anticipated that we will identify novel differentiation protocols that lead to generation of functional chondrocytes for intra-articular transplantation and regeneration of damaged articular joints. Therefore our project has the potential to combat this severe social burden by contributing to the ongoing search for therapy targets and furthermore obtained results can be the starting point for novel therapeutic interventions.

Keywords:
amniotic fluid stem cells, autologouse chondrocytes, chondrogenic differentiation, mechanistic target of rapamycin