Encapsulation of recombinant cells with a novel magnetized alginate for magnetic resonance imaging.
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.
Shen
Feng
F
Department of Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Li
Anna Aihua
AA
Gong
Yong-Kuan
YK
Somers
Sat
S
Potter
Murray A
MA
Winnik
Françoise M
FM
Chang
Patricia L
PL
D000464:Alginates; D000818:Animals; D001402:B-Lymphocytes; D001672:Biocompatible Materials; D002214:Capsules; D005164:Factor IX / Q000008:administration & dosage; D015316:Genetic Therapy / Q000379:methods*; D005966:Glucuronidase / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000032:analysis; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D008422:Materials Testing; D051379:Mice; D010539:Permeability; D014162:Transfection
D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D007074:Immunoglobulin G; D005164:Factor IX; D007501:Iron; D005966:Glucuronidase