Ferumoxytol Labeling of Human Neural Progenitor Cells for Diagnostic Cellular Tracking in the Porcine Spinal Cord with Magnetic Resonance Imaging.
We report on the diagnostic capability of magnetic resonance imaging (MRI)-based tracking of ferumoxytol-labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC-FLowand hNPC-FHigh) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol-labeled grafts were tracked in vivo up to 105 days after transplantation with MRI. Injection accuracy was assessed in vivo at day 14 and was predictive of "on" or "off" target cell graft location assessed by histology. No difference in long-term cell survival, assessed by quantitative stereology, was observed among hNPC-FLow, hNPC-FHigh, or control grafts. Histological iron colocalized with MRI signal and engrafted human nuclei. Furthermore, the ferumoxytol-labeled cells retained nanoparticles and function in vivo. This approach represents an important leap forward toward facilitating translation of cell-tracking technologies to clinical trials by providing a method of assessing transplantation accuracy, delivered dose, and potentially cell survival. Stem Cells Translational Medicine 2017;6:139-150.
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Jason J
JJ
Lamanna
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.
Juanmarco
J
Gutierrez
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.
Lindsey N
LN
Urquia
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.
C Victor
CV
Hurtig
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Elman
E
Amador
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.
Natalia
N
Grin
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Clive N
CN
Svendsen
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.
Thais
T
Federici
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.|Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, Georgia, USA.
John N
JN
Oshinski
Department of Neurosurgery, School of Medicine, Emory University, Atlanta, Georgia, USA.|Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Nicholas M
NM
Boulis
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D058948:Cell Tracking; D004705:Endocytosis; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D013116:Spinal Cord / Q000166:cytology*; D013194:Staining and Labeling; D013552:Swine
D007501:Iron; D052203:Ferrosoferric Oxide
Cell transplantation; Clinical translation; In vivo tracking; Magnetic resonance imaging; Neural stem cell; Pig model; Spinal cord; Stem cell transplantation