Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells.
The ability to track the distribution and differentiation of progenitor and stem cells by high-resolution in vivo imaging techniques would have significant clinical and research implications. We have developed a cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles. The particles are efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10-30 pg of superparamagnetic iron per cell. Iron incorporation did not affect cell viability, differentiation, or proliferation of CD34+ cells. Following intravenous injection into immunodeficient mice, 4% of magnetically CD34+ cells homed to bone marrow per gram of tissue, and single cells could be detected by magnetic resonance (MR) imaging in tissue samples. In addition, magnetically labeled cells that had homed to bone marrow could be recovered by magnetic separation columns. Localization and retrieval of cell populations in vivo enable detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells.
Lewin
M
M
Center of Molecular Imaging Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Carlesso
N
N
Tung
C H
CH
Tang
X W
XW
Cory
D
D
Scadden
D T
DT
Weissleder
R
R
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D005290:Ferric Compounds; D015696:Gene Products, tat / Q000737:chemistry / Q000493:pharmacokinetics*; D015497:HIV-1; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009420:Nervous System / Q000166:cytology; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D013234:Stem Cells / Q000166:cytology; D014183:Transplantation, Heterologous; D054322:tat Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D018952:Antigens, CD34; D005290:Ferric Compounds; D015696:Gene Products, tat; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; C000499:ferric oxide