Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study.
BACKGROUND
This study aimed to determine the homing potential and fate of epidermal neural crest stem cells (eNCSCs) derived from hair follicles, and bone marrow-derived stem cells (BMSCs) of mesenchymal origin, in a lipopolysaccharide (LPS)-induced inflammatory lesion model in the rat brain. Both eNCSCs and BMSCs are easily accessible from adult tissues by using minimally invasive procedures and can differentiate into a variety of neuroglial lineages. Thus, these cells have the potential to be used in autologous cell-replacement therapies, minimizing immune rejection, and engineered to secrete a variety of molecules.


METHODS
Both eNCSCs and BMSCs were prelabeled with iron-oxide nanoparticles (IO-TAT-FITC) and implanted either onto the corpus callosum in healthy or LPS-lesioned animals or intravenously into lesioned animals. Both cell types were tracked longitudinally in vivo by using magnetic resonance imaging (MRI) for up to 30 days and confirmed by postmortem immunohistochemistry.


RESULTS
Transplanted cells in nonlesioned animals remained localized along the corpus callosum. Cells implanted distally from an LPS lesion (either intracerebrally or intravenously) migrated only toward the lesion, as seen by the localized MRI signal void. Fluorescence microscopy of the FITC tag on the nanoparticles confirmed the in vivo MRI data,


CONCLUSIONS
This study demonstrated that both cell types can be tracked in vivo by using noninvasive MRI and have pathotropic properties toward an inflammatory lesion in the brain. As these cells differentiate into the glial phenotype and are derived from adult tissues, they offer a viable alternative autologous stem cell source and gene-targeting potential for neurodegenerative and demyelinating pathologies.
Jackson
Johanna S
JS
Stem Cell Imaging, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK. johanna.jackson@med.lu.se
Golding
Jon P
JP
Chapon
Catherine
C
Jones
William A
WA
Bhakoo
Kishore K
KK
D061605:Administration, Intravenous; D000818:Animals; D001854:Bone Marrow Cells; D001921:Brain / Q000166:cytology / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000628:therapy*; D002454:Cell Differentiation; D002465:Cell Movement; D064987:Cell- and Tissue-Based Therapy; D003337:Corpus Callosum / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000628:therapy; D005290:Ferric Compounds; D018859:Hair Follicle / Q000166:cytology; D008070:Lipopolysaccharides; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles; D008856:Microscopy, Fluorescence; D009432:Neural Crest / Q000166:cytology; D019636:Neurodegenerative Diseases / Q000628:therapy; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055757:SOXE Transcription Factors / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D014182:Transplantation, Autologous
D005290:Ferric Compounds; D008070:Lipopolysaccharides; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat; C000499:ferric oxide