Long-Term MRI Cell Tracking after Intraventricular Delivery in a Patient with Global Cerebral Ischemia and Prospects for Magnetic Navigation of Stem Cells within the CSF

Abstract

BackgroundThe purpose of the study was to evaluate the long-term clinical tracking of magnetically labeled stem cells after intracerebroventricular transplantation as well as to investigate in vitro feasibility for magnetic guidance of cell therapy within large fluid compartments.MethodAfter approval by our Institutional Review Board, an 18-month-old patient, diagnosed as being in a vegetative state due to global cerebral ischemia, underwent cell transplantation to the frontal horn of the lateral ventricle, with umbilical cord blood-derived stem cells labeled with superparamagnetic iron oxide (SPIO) contrast agent. The patient was followed over 33 months with clinical examinations and MRI. To evaluate the forces governing the distribution of cells within the fluid compartment of the ventricular system in vivo, a gravity-driven sedimentation assay and a magnetic field-driven cell attraction assay were developed in vitro.ResultsTwenty-four hours post-transplantation, MR imaging (MRI) was able to detect hypointense cells in the occipital horn of the lateral ventricle. The signal gradually decreased over 4 months and became undetectable at 33 months. In vitro, no significant difference in cell sedimentation between SPIO-labeled and unlabeled cells was observed (p = NS). An external magnet was effective in attracting cells over distances comparable to the size of human lateral ventricles.ConclusionsMR imaging of SPIO-labeled cells allows monitoring of cells within lateral ventricles. While the initial biodistribution is governed by gravity-driven sedimentation, an external magnetic field may possibly be applied to further direct the distribution of labeled cells within large fluid compartments such as the ventricular system.

The long-term fate of mesenchymal stem cells labeled with magnetic resonance imaging-visible polymersomes in cerebral ischemia

“…9 At present, in vivo real-time tracking of stem cells has been well established in ischemic stroke, which is mainly based on MRI of superparamagnetic iron oxide nanoparticles (SPION)-labeled stem cells. [10][11][12] However, SPION-based MRI does not provide reliable information on long-term cell viability and might overestimate the survival of SPIONlabeled therapeutic MSCs in myocardial infarction. 13,14 The ability of SPION-based MRI to reliably evaluate long-term cell engraftment and survival remains controversial.…”

Theranostic Magnetic Nanostructures (MNS) for Cancer

“…In contrast to scintigraphic imaging, MRI allowed assessment of the accuracy of dendritic cell delivery and of inter- and intranodal cell migration patterns [139–143]. Recently, Bulte et al evaluated the long-term clinical tracking of MNS labeled stem cells after intracerebroventricular transplantation in an 18-month-old patient with global cerebral ischemia [144]. Twenty-four hours post-transplantation, MRI was able to detect hypointense cells in the occipital horn of the lateral ventricle.…”

Gaining Mechanistic Insights into Cell Therapy Using Magnetic Resonance Imaging

“…The preferred contrast agent for Bcell tracking^by MRI is iron oxide, as it can provide a robust signal that can be detected against most tissue backgrounds for over 1 year [25]. This approach has found some clinical translation to assess the migration of neural progenitors after intraparenchymal administration into a patient with traumatic brain injury [26], as well as umbilical cord blood-derived stem cells upon intra-cerebroventricular injection into a patient with global cerebral ischemia [27]. However, small bleeds and air can induce an equivalent hypointense signal as that caused by iron oxide agents and lead to false positives.…”