Magnetic Resonance Imaging-Guided Delivery of Neural Stem Cells Into the Basal Ganglia of Nonhuman Primates Reveals a Pulsatile Mode of Cell Dispersion.

: Optimal stem cell delivery procedures are critical to the success of the cell therapy approach. Variables such as flow rate, suspension solution, needle diameter, cell density, and tissue mechanics affect tissue penetration, backflow along the needle, and the dispersion and survival of injected cells during delivery. Most cell transplantation centers engaged in human clinical trials use custom-designed cannula needles, syringes, or catheters, sometimes precluding the use of magnetic resonance imaging (MRI)-guided delivery to target tissue. As a result, stem cell therapies may be hampered because more than 80% of grafted cells do not survive the delivery-for example, to the heart, liver/pancreas, and brain-which translates to poor patient outcomes. We developed a minimally invasive interventional MRI (iMRI) approach for intraoperatively imaging neural stem cell (NSC) delivery procedures. We used NSCs prelabeled with a contrast agent and real-time magnetic resonance imaging to guide the injection cannula to the target and to track the delivery of the cells into the putamen of baboons. We provide evidence that cell injection into the brain parenchyma follows a novel pulsatile mode of cellular discharge from the delivery catheter despite a constant infusion flow rate. The rate of cell infusion significantly affects the dispersion and viability of grafted cells. We report on our investigational use of a frameless navigation system for image-guided NSC transplantation using a straight cannula. Through submillimeter accuracy and real-time imaging, iMRI approaches may improve the safety and efficacy of neural cell transplantation therapies.

SIGNIFICANCE: Optimal stem cell delivery procedures are critical to the success of the cell therapy approach. A minimally invasive interventional magnetic resonance imaging approach was developed for imaging intraoperatively neural stem cell (NSC) delivery procedures. NSC delivery was imaged in real time in nonhuman primate forebrain. Evidence indicates that cell injection follows novel pulsatile mode of dispersion and that the rate of cell infusion significantly affects the dispersion and viability of grafted cells. This approach will improve the safety and efficacy of neural transplantation and address some of the current bottlenecks in translating stem cell therapies to the clinic.