Longitudinal evaluation of MPIO-labeled stem cell biodistribution in glioblastoma using high resolution and contrast-enhanced MR imaging at 14.1 tesla.
To optimize the development of stem cell (SC)-based therapies for the treatment of glioblastoma (GBM), we compared the pathotropism of 2 SC sources, human mesenchymal stem cells (hMSCs) and fetal neural stem cells (fNSCs), toward 2 orthotopic GBM models, circumscribed U87vIII and highly infiltrative GBM26. High resolution and contrast-enhanced (CE) magnetic resonance imaging (MRI) were performed at 14.1 Tesla to longitudinally monitor the in vivo location of hMSCs and fNSCs labeled with the same amount of micron-size particles of iron oxide (MPIO). To assess pathotropism, SCs were injected in the contralateral hemisphere of U87vIII tumor-bearing mice. Both MPIO-labeled SC types exhibited tropism to tumors, first localizing at the tumor edges, then in the tumor masses. MPIO-labeled hMSCs and fNSCs were also injected intratumorally in mice with U87vIII or GBM26 tumors to assess their biodistribution. Both SC types distributed throughout the tumor in both GBM models. Of interest, in the U87vIII model, areas of hyposignal colocalized first with the enhancing regions (ie, regions of high vascular permeability), consistent with SC tropism to vascular endothelial growth factor. In the GBM26 model, no rim of hyposignal was observed, consistent with the infiltrative nature of this tumor. Quantitative analysis of the index of dispersion confirmed that both MPIO-labeled SC types longitudinally distribute inside the tumor masses after intratumoral injection. Histological studies confirmed the MRI results. In summary, our results indicate that hMSCs and fNSCs exhibit similar properties regarding tumor tropism and intratumoral dissemination, highlighting the potential of these 2 SC sources as adequate candidates for SC-based therapies.
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Myriam M
MM
Chaumeil
Beatrice
B
Gini
Huijun
H
Yang
Akio
A
Iwanami
Subramaniam
S
Sukumar
Tomoko
T
Ozawa
Russel O
RO
Pieper
Paul S
PS
Mischel
C David
CD
James
Mitchel S
MS
Berger
Sabrina M
SM
Ronen
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005290:Ferric Compounds; D053686:Fetal Stem Cells; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D059630:Mesenchymal Stem Cells; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental; D058953:Neural Stem Cells; D059906:Neuroimaging; D033581:Stem Cell Transplantation
D005290:Ferric Compounds; C000499:ferric oxide