Implanting recombinant cells encapsulated in
alginate microcapsules to express therapeutic
proteins has been proven effective in treating several mouse models of human diseases (
neurological disorders,
dwarfism,
hemophilia,
lysosomal storage disease, and
cancer). In anticipation of clinical application, we have reported the synthesis and characterization of a magnetized ferrofluid
alginate that potentially allows tracking of these
microcapsules in vivo by magnetic resonance imaging (MRI). We now report the properties of these ferrofluid
microcapsules important for applications in gene therapy. When a mouse myoblast cell line was encapsulated in these
microcapsules, it showed similar viability as in regular unmodified
alginate capsules, both in vitro and in vivo, in mice. The permeability of these magnetized
microcapsules, a critical parameter for immunoisolation devices, was comparable to that of classic
alginate in the transit of various recombinant molecules of various molecular masses (human
factor IX, 65 kDa; murine
IgG, 150 kDa; and
beta-glucuronidase, 300 kDa). When followed by MRI in vitro and in vivo, the ferrofluid
microcapsules remained intact and visible for extended periods, allowing quantitative monitoring of
microcapsules. At autopsy, the ferrofluid
microcapsules were mostly free within the intraperitoneal cavities, with no overt inflammatory response. Serological analyses demonstrated a high level of biocompatibility comparable to that of unmodified
alginate. In conclusion, ferrofluid-enhanced
alginate microcapsules are comparable to classic
alginate microcapsules in permeability and biocompatibility. Their visibility and stability to MRI monitoring permitted qualitative and quantitative tracking of the implanted
microcapsules without invasive surgery. These properties are important advantages for the application of immunoisolation devices in human gene therapy.