Page 16 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Chapter 1
leading to major societal impact (42). The presence of inflammation in the joint is a cause or an exacerbating factor for OA, for which there is no effective treatment currently. The focus is now primarily on pain reduction, so knowledge on how to delay or stop inflammatory damage may be crucial for the development of more curative treatment strategies. A possible treatment could be the modulation of the functional state of the inflammatory cells. The aims of our study described in this thesis were 1) to determine how macrophage phenotypes and monocyte subsets vary with time after destabilization of the medial meniscus; 2) to investigate associations between monocyte subsets or macrophage phenotypes and OA features 3) in vivo macrophage visualisation during the course of OA (43).
Labels for cell imaging
There are many types of imaging labels with different size, shape, composition and functionality (44), including liposomes, polymers, dextran coated particles, antibodies and peptides. When injected in the bloodstream these carriers travel throughout the body and can end up in extravascular spaces, followed by binding to and/or uptake in the targeted cells. The fact that carriers can bind and or be taken up by cells has enabled new ways of imaging of organs, tumours and other tissues in the body (45, 46).
Non targeted iron oxide particles
The most commonly applied and easiest way to achieve spontaneous uptake of an imaging particle is by exposing the cells to the labelling agent in culture. This may require additional use of a transfection agent (47). The cells then actively incorporate the particles through endocytotic pathways; the particles generally end up in endosomal compartments (Fig. 1). The now cell-associated labelling agent serves as the signaling beacon by which transplanted cells can be identified in imaging studies (48-51).
Particulate label types used in this thesis are two types of iron oxide particles: super paramagnetic iron oxide particles (SPIO) and micro particles of iron oxide (MPIO) which provide high detection sensitivity. SPIO particles have a particle diameter between 80 and 150nm, consisting of an iron oxide core of 4 nm with a low-molecular-weight dextran coating (52-54). MPIO particles are composed of polystyrene–divinyl benzene polymer micro spheres containing
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