No abstract

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‐FLow and 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

This series supports the functional safety of various injection volumes and numbers in the spinal cord and gives critical insight into important safety thresholds. These results are relevant to all translational programs delivering cell therapeutics to the spinal cord.

Background: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks. The objective of this study was to present the proof of principle for minimally invasive, percutaneous transplantation of stem cells into the spinal cord parenchyma of live minipigs under MR guidance. Methods: An MR-compatible spine injection platform was developed to work with the ClearPoint SmartFrame system (MRI Interventions Inc.). The system was attached to the spine of 2 live minipigs, a percutaneous injection cannula was advanced into the spinal cord under MR guidance, and cells were delivered to the cord. Results: A graft of 2.5 × 10⁶ human (n = 1) or porcine (n = 1) neural stem cells labeled with ferumoxytol nanoparticles was transplanted into the ventral horn of the spinal cord with MR guidance in 2 animals. Graft delivery was visualized with postprocedure MRI, and characteristic iron precipitates were identified in the spinal cord by Prussian blue histochemistry. Grafted stem cells were observed in the spinal cord of the pig injected with porcine neural stem cells. No postoperative morbidity was observed in either animal. Conclusion: This report supports the proof of principle for transplantation and visualization of pharmacological or biological agents into the spinal cord of a large animal under the guidance of MRI.