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30 September 2010 Nanosystems Initiative Munich

Regeneration of osteoarthritis using nanoparticles

EU-funded project at Klinikum rechts der Isar develops new methods

The European Union is funding a research project coordinated by the Klinikum rechts der Isar der Technischen Universität München (TUM), Munich, Germany with €3.2m. The project develops new methods for treatment of osteoarthritis. Researchers aim at inducing the self healing capacity of damaged cartilage and bone by coordinated cooperation/interaction of gene vectors, mesenchymal stem cells, polymers and magnetic nanoparticles.

Degenerative Arthritis affects approximately every fourth German. Looking at the population aged 65 and higher every second person suffers from the disease, with increasing degeneration of cartilage and ultimately destruction of the underlying bone as well. The etiology of osteoarthritis (OA) is still unknown. Therapy is currently mainly symptomatic with reduction of pain and inflammation, but not restorative, and is often ending in total joint replacement. The newly started research project GAMBA (Gene Activated Matrices for Bone and Cartilage Regeneration in Arthritis) is investigating new methods to induce regenerative processes within the body.

Project coordinator Dr. Martina Anton and co-initiator Dr. Christian Plank (NIM member) at the Institute for Experimental Oncology and Therapy Research (Director: Prof. Bernd Gänsbacher) at Klinikum rechts der Isar have assembled a team of international specialists with nine rearch groups from Germany, France, Ireland, Italy, the Netherlands and Switzerland. The international partners all have their special expertises contributing to the consortium as a whole. The team at the Klinikum rechts der Isar e.g. has experience in using biocompatible magnetic nanoparticles and the development of gene vectors supplying cells with genes for therapeutic purposes.

“GAMBA combines different aspects of osteoarthritis therapy in a unique fashion“ explains Dr. Martina Anton. Theses new strategies will be developed experimentally in the next three years. Researchers aim at inducing self-healing capacity of patients by use of mesenchymal stem cells (precursors for bone, cartilage and adipose tissue cells). Using gene vectors cells will be equipped with new genetic information that will allow for production of therapeutically relevant proteins in a transiently. Ideally a three-fold combination will be developed addressing inflammation as well as cartilage and bone repair. To achieve this researchers will use interleukin-10 for reduction of inflammation, BMP-2 (bone morphogenetic protein) for regeneration of bone and TGF-ß (transforming growth factor) for regeneration of cartilage. The reading of these genetic codes will be started and regulated from the outside by chemical and physical cues.

Dr. Christian Plank explains that local and temporal regulation are essentials of GAMBA: “By being able to specifically switch on and off gene vector activity and embedding of vectors and cells in synthetic hyaluronic acid gels and bone substitute materials we aim at limiting of gene vector action to the diseased tissue.” In this manner e.g. magnetic nanoparticles warm up, when placed in a magnetic field, which in turn leads to activation of a heat shock (HSP70) gene switch that regulates production of BMP-2. At the same time the synthetic hyaluronic acid gel in which the stem cells are embedded will shrink leading to increased release of TGF-ß gene vector.

Dr. Martina Anton cautions excessive expectations: „It might well occur that we can only induce one or two of the intended three healing processes.“ However, if as hoped for the results point to promising methods, in the next step researchers will investigate how patients can profit from these new results.

Another essential part of the project deals with involving patients and citizens early in the research. Therefore novel ways of outreach methods called patient and citizen panels will be used. These will be held indifferent countries in order to enhance awareness of nanomedicine in the public and take into account public expectations and reservations. Aim is to start early on a public debate on ethical, legal and societal issues connected to the research project.

Source: Nanosystems Initiative Munich /...

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