title: 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.
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Present address: Department of Bioengineering, University of California, Davis, Davis, California, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Silvestrini
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Dali
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Radiology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Martin
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Department of Surgery, Veteran's Affairs Medical Center, San Francisco, California, USA.
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Coppes
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Department of Surgery, Veteran's Affairs Medical Center, San Francisco, California, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Mann
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Department of Surgery, Veteran's Affairs Medical Center, San Francisco, California, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Larson
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Starr
authors.affiliation: Buck Institute for Research on Aging, Novato, California, USA.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Nalin
authors.initials: N
authors.lastname: Gupta
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Department of Surgery, Veteran's Affairs Medical Center, San Francisco, California, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Panter
authors.affiliation: Department of Bioengineering, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
authors.affiliation: 1] Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA [2] Department of Surgery, Veteran's Affairs Medical Center, San Francisco, California, USA [3] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, San Francisco, California, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lim
mesh_terms: D000818:Animals; D002102:Cadaver; D002404:Catheterization; D017690:Cell Transplantation; D003342:Corpus Striatum / Q000601:surgery; D005260:Female; D006801:Humans; D053783:Magnetic Resonance Imaging, Interventional / Q000295:instrumentation / Q000379:methods*; D011699:Putamen / Q000601:surgery; D013238:Stereotaxic Techniques / Q000295:instrumentation*; D013552:Swine