Interventional Magnetic Resonance Imaging-guided Cell Transplantation Into the Brain With Radially Branched Deployment

Abstract

Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI-guided RBD functioned as an "add-on" to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI-guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases.

Real-Time Intraoperative MRI Intracerebral Delivery of Induced Pluripotent Stem Cell-Derived Neurons

“…Beyond assessing the viability of the cells after passing through the system 20 , we were concerned as to whether the cells were affected by the time elapsed after their upload, as the best-planned surgery can run into delays. Our experiment demonstrated that cell viability is acceptable up to 2 h after being in the system, although some adhesion of neurospheres was observed.…”

The role of nonhuman primate models in the development of cell-based therapies for Parkinson’s disease

“…For example, great strides have been made towards the development and improvement of intraoperative MRI (iMRI) methods (Mislow et al 2009 ). Silvestrini et al (Silvestrini et al 2015 ) used real-time iMRI (RT-iMRI) for cell transplantation into a swine and cadaveric human head as a concept for application in the human brain. The platform technology utilizes a radially branched deployment strategy to access multi-directional deposit sites along a single cannula insertion tract.…”

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease

“…Interventional MRI (iMRI) is a stereotactic neurosurgical technique that can be used to accurately implant DBS leads and deliver biologics with “real‐time” MR guidance and monitoring . For instance, with iMRI, the same skull‐mounted aiming device can be used for gene therapy infusion or cell delivery before DBS lead implantation . Given that the typical trajectories used for DBS lead implantation and biologic delivery to relevant PD brain targets are similar (Fig.…”

“…13,32 For instance, with iMRI, the same skull-mounted aiming device can be used for gene therapy infusion or cell delivery before DBS lead implantation. 33 Given that the typical trajectories used for DBS lead implantation and biologic delivery to relevant PD brain targets are similar (Fig. 1B), one burr hole per hemisphere is likely to suffice.…”