Magnetic resonance imaging-guided delivery of neural stem cells into the basal ganglia ofnonhuman primates reveals a pulsatile mode of cell dispersion

Optimal stemcell delivery procedures are critical to the success of the cell therapy approach. Variables such as flowrate, suspension solution, needle diameter, cell density, and tissuemechanics affect tissue penetration, back flowalong the needle, and the dispersion and survival of injected cells during delivery. Most cell transplantationcenters engaged inhuman clinical trials use custom-designedcannulaneedles, 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.Wedeveloped a minimally invasive interventionalMRI (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.