Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on collagen scaffolds-relevance to tissue engineering.
Mesenchymal stem cells (MSCs) are a promising candidate cell for tissue engineering. Magnetic resonance imaging (MRI) has been proven effective in visualizing iron-labeled stem cells; however, the efficiency of this approach for visualization of cells seeded on scaffolds intended for use as tissue-engineered heart valves has not been assessed. MSCs were labeled by incubating for 48 h with ferumoxide and poly-L-lysine as transfecting agent. Any detrimental effect of iron labeling on cell viability, proliferation, and differentiation was examined using appropriate functional assays. Change in the nuclear magnetic relaxation properties of labeled cells was determined using in vitro relaxometry of cells seeded in 3-dimensional collagen gels. Images of labeled and non-labeled cells seeded onto 1% type I bovine collagen scaffolds were obtained using MRI. The presence of intracellular iron in labeled cells was demonstrated using Prussian blue staining, confocal microscopy, and electron microscopy. Cell viability, proliferation, and differentiation were comparable in labeled and non-labeled cells. The T2 relaxation time was 40% to 50% shorter in ferumoxide-labeled cells. Labeled cells seeded on scaffolds appeared as areas of reduced signal intensity in T2 weighted images. Ferumoxide labeling persisted and remained effective even on scans performed 4 weeks after the labeling procedure. Ferumoxide labeling of human MSCs seeded on collagen scaffolds is an effective, non-toxic technique for visualization of these cells using MRI. This technique appears promising for cell tracking in future tissue-engineering applications.
Terrovitis
John V
JV
Heart Science Centre, Harefield Hospital, Imperial College, London, United Kingdom. john.terrovitis@gmail.com
Bulte
Jeff W M
JW
Sarvananthan
Sajiram
S
Crowe
Lindsey A
LA
Sarathchandra
Padmini
P
Batten
Puspa
P
Sachlos
Eleftherios
E
Chester
Adrian H
AH
Czernuszka
Jan T
JT
Firmin
David N
DN
Taylor
Patricia M
PM
Yacoub
Magdi H
MH
D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D010087:Oxides; D023822:Tissue Engineering / Q000379:methods*
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D003094:Collagen; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide