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

被引:15
作者
Malloy, Kristen E. [1 ,2 ]
Li, Jinqi [2 ]
Choudhury, Gourav R. [1 ]
Torres, April [1 ]
Gupta, Shruti [3 ]
Kantorak, Chris [3 ]
Goble, Tim [3 ]
Fox, Peter T. [2 ]
Clarke, Geoffrey D. [2 ]
Daadi, Marcel M. [1 ,2 ]
机构
[1] Texas Biomed Res Inst, Southwest Natl Primate Res Ctr, POB 760549, San Antonio, TX 78245 USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Radiol, San Antonio, TX 78229 USA
[3] MRI Intervent Inc, Irvine, CA USA
关键词
Interventional magnetic resonance imaging; Stem cell delivery; Cell flow; Nonhuman primate; ClearPoint system; Rheology; Real-time interventional magnetic resonance imaging guided cell transplantation; CONVECTION-ENHANCED DELIVERY; RADIALLY BRANCHED DEPLOYMENT; DEEP BRAIN-STIMULATION; DRUG-DELIVERY; PARKINSONS-DISEASE; INTERVENTIONAL MRI; INFUSION; TRANSPLANTATION; PLACEMENT; STRIATUM;
D O I
10.5966/sctm.2016-0269
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 inhuman 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. Wedeveloped 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. (C) STEM CELLS TRANSLATIONAL MEDICINE
引用
收藏
页码:877 / 885
页数:9
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