title: Clinically viable magnetic poly(lactide-co-glycolide) particles for MRI-based cell tracking.
abstract: OBJECTIVE
  To design, fabricate, characterize, and in vivo assay clinically viable magnetic particles for MRI-based cell tracking.
  
  
  METHODS
  Poly(lactide-co-glycolide) (PLGA) encapsulated magnetic nano and microparticles were fabricated. Multiple biologically relevant experiments were performed to assess cell viability, cellular performance, and stem cell differentiation. In vivo MRI experiments were performed to separately test cell transplantation and cell migration paradigms, as well as in vivo biodegradation.
  
  
  RESULTS
  Highly magnetic nano (∼100 nm) and microparticles (∼1-2 µm) were fabricated. Magnetic cell labeling in culture occurred rapidly achieving 3-50 pg Fe/cell at 3 h for different particles types, and >100 pg Fe/cell after 10 h, without the requirement of a transfection agent, and with no effect on cell viability. The capability of magnetically labeled mesenchymal or neural stem cells to differentiate down multiple lineages, or for magnetically labeled immune cells to release cytokines following stimulation, was uncompromised. An in vivo biodegradation study revealed that NPs degraded ∼80% over the course of 12 weeks. MRI detected as few as 10 magnetically labeled cells, transplanted into the brains of rats. Also, these particles enabled the in vivo monitoring of endogenous neural progenitor cell migration in rat brains over 2 weeks.
  
  
  CONCLUSIONS
  The robust MRI properties and benign safety profile of these particles make them promising candidates for clinical translation for MRI-based cell tracking.
authors.affiliation: Molecular and Cellular MRI Laboratory, Magnetic Resonance Research Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Dorit
authors.initials: D
authors.lastname: Granot
authors.forename: Michael K
authors.initials: MK
authors.lastname: Nkansah
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Bennewitz
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Tang
authors.forename: Eleni A
authors.initials: EA
authors.lastname: Markakis
authors.forename: Erik M
authors.initials: EM
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D003287:Contrast Media / Q000138:chemical synthesis; D005260:Female; D007089:Image Enhancement / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid