We report on a novel and straightforward magnetic cell labeling approach that combines three FDA-approved drugs, ferumoxytol (F), heparin (H) and protamine (P) in serum free media to form self-assembling nanocomplexes that effectively label cells for in vivo MRI. We observed that the HPF nanocomplexes were stable in serum free cell culture media. HPF nanocomplexes exhibited a three-fold increase in T2 relaxivity compared to F. Electron Microscopy revealed internalized HPF within endosomes, confirmed by Prussian blue staining of labeled cells. There was no long-term effect or toxicity on cellular physiology or function of HPF-labeled hematopoietic stem cells, bone marrow stromal cells, neural stem cells, and T-cells when compared to controls. In vivo MRI detected 1000 HPF-labeled cells implanted in rat brains. HPF labeling method should facilitate the monitoring by MRI of infused or implanted cells in clinical trials.

Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.