Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells.
Tracking transplanted stem cells using magnetic resonance imaging (MRI) could offer biologic insight into homing and engraftment. Ultrasmall dextran-coated iron oxide particles have previously been developed for uptake into cells to allow MRI tracking. We describe a new application of much larger, micron-scale, iron oxide magnetic particles with enhanced MR susceptibility, which enables detection of single cells at resolutions that can be achieved in vivo. In addition, these larger particles possess a fluorophore for histologic confirmation of cell distribution. We demonstrate highly efficient, nontoxic, endosomal uptake of these particles into hematopoietic CD34+ cells and mesenchymal stem cells documented by confocal and electron microscopy. Labeled cells retain biologic activity with preservation of colony-forming ability and differentiation capacity. MRI studies could detect labeled CD34+ cells and mesenchymal stem cells (MSCs) at single cell resolution. This appears to be a promising tool for serial noninvasive monitoring of in vivo cell homing and localization using MRI.
Hinds
Kathleen A
KA
Hematology Branch, Laboratory of Molecular Biology, Laboratory National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD 20892, USA.
Hill
Jonathan M
JM
Shapiro
Erik M
EM
Laukkanen
Mikko O
MO
Silva
Alfonso C
AC
Combs
Christian A
CA
Varney
Timothy R
TR
Balaban
Robert S
RS
Koretsky
Alan P
AP
Dunbar
Cynthia E
CE
D000818:Animals; D018952:Antigens, CD34; D002454:Cell Differentiation; D002455:Cell Division; D011992:Endosomes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008648:Mesoderm / Q000166:cytology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010012:Osteogenesis; D010087:Oxides / Q000493:pharmacokinetics*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013552:Swine
D018952:Antigens, CD34; D010087:Oxides; C094094:carboxydextran-coated magnetic iron oxide particles; D007501:Iron