Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI.
Noninvasive monitoring of stem cells, using high-resolution molecular imaging, will be instrumental to improve clinical neural transplantation strategies. We show that labeling of human central nervous system stem cells grown as neurospheres with magnetic nanoparticles does not adversely affect survival, migration, and differentiation or alter neuronal electrophysiological characteristics. Using MRI, we show that human central nervous system stem cells transplanted either to the neonatal, the adult, or the injured rodent brain respond to cues characteristic for the ambient microenvironment resulting in distinct migration patterns. Nanoparticle-labeled human central nervous system stem cells survive long-term and differentiate in a site-specific manner identical to that seen for transplants of unlabeled cells. We also demonstrate the impact of graft location on cell migration and describe magnetic resonance characteristics of graft cell death and subsequent clearance. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation.
Guzman
Raphael
R
Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive R200, Stanford, CA 94305-5327, USA.
Uchida
Nobuko
N
Bliss
Tonya M
TM
He
Dongping
D
Christopherson
Karen K
KK
Stellwagen
David
D
Capela
Alexandra
A
Greve
Joan
J
Malenka
Robert C
RC
Moseley
Michael E
ME
Palmer
Theo D
TD
Steinberg
Gary K
GK
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003911:Dextrans; D005240:Feasibility Studies; D052203:Ferrosoferric Oxide; D006801:Humans; D007276:Injections, Intraventricular; D007501:Iron / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008991:Monitoring, Physiologic; D053758:Nanoparticles; D009474:Neurons / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology / Q000637:transplantation*; D010087:Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000628:therapy; D014183:Transplantation, Heterologous
D015415:Biomarkers; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide