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ePaper created 2017-03-14, 10:25:37 | version 1.49.03
HEALTH H2N HO HO HO O O NH2 O O H2N OH 1 NH2 OH HO O O O HO IRON OXIDE NANOPARTICLES FOR REGENERATIVE MEDICINE M ar ia Ste inke, Te re s a K ilian, H e ike Wa ll e s Biocompatible iron oxide nanoparticles We have succeeded in identifying a particle prototype (M4E) that is internalized by MSCs. M4E particles have a hydrody- namic diameter of 115 nm and consist of an iron oxide core and an amino-functionalized dextran shell (Fig. 1). In in vitro cultures, almost 100 percent of the MSCs internalized the M4E particles (Fig. 2). They are passed on to both daughter cells during cell division, which theoretically enables long-term cell tracking. However, the stem cell labeling dramatically de- creases within a few days if they are cultured under 2D condi- tions. If the labeled MSCs are cultured on a three-dimensional scaffold serving as a tissue environment, however, labeled cells can be veriied for up to six weeks. Another technology enabling us to track labeled MSCs for up to six weeks is non- invasive magnetic particle spectroscopy, which is based on the same physical principle as MPI. M4E particles do not impact viability, growth or proliferation of MSCs. Furthermore, M4E particles do not trigger any genotoxic effects [1]. Based on these indings, the criteria we deined regarding biocompat- ibility have been met. Non-invasive technologies for regenerative medicine In the research area of regenerative medicine, science focuses on repairing damaged tissue using therapeutic cells, which include mesenchymal stem cells (MSCs). MSCs have a capac- ity for self-renewal and are capable of differentiating into multiple cell types including osteocytes and chondrocytes. To localize and track stem cells after they have been injected or implanted into the body, they can be labeled with superpara- magnetic iron oxide nanoparticles serving as a contrast agent. For non-invasive localization, magnetic resonance imaging (MRI) has been used in both pre-clinical and clinical studies. However, the cellular resolution is often not suficient with this procedure. Imaging with magnetic particles As of late, a new procedure has been available for pre-clinical studies: magnetic particle imaging (MPI). This procedure has a higher temporal and spatial resolution as well as a higher sensitivity than MRI. The use of iron oxide nanoparticles for the non-invasive localization of stem cells is currently limited: Due to a lack of biocompatibility, many particle prototypes fail in the two-dimensional cell culture model. Furthermore, cell labeling often does not last longer than a few days, which makes long-term tracking in the body impossible. As part of the EU-funded project “IDEA – Identiication, homing and monitoring of therapeutic cells for regenerative medicine – Identify, Enrich, Accelerate”, our goal is to develop iron oxide particles that are biocompatible and suitable for imaging in long-term studies using MPI. 5 4