Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19F Magnetic Resonance Imaging. (7th January 2019)

• Record Type: Journal Article
• Authors: Richard, Jean-Philippe; Hussain, Uzma; Gross, Sarah; Taga, Arens; Kouser, Mehreen; Almad, Akshata; Campanelli, James T.; Bulte, Jeff W.M.; Maragakis, Nicholas J.
• Is Part Of: Stem cells translational medicine. Volume 8:Number 4(2019)
• Page Start: 355
• Page End: 365
• Publication Date: 2019-01-07
• Subjects: MRI -- Cell tracking -- Fluorine-19 -- 19F -- Perfluorocarbon -- Stem cell -- Transplantation; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.18-0094
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: One of the fundamental limitations in assessing potential efficacy in Central Nervous System (CNS) transplantation of stem cells is the capacity for monitoring cell survival and migration noninvasively and longitudinally. Human glial-restricted progenitor (hGRP) cells (Q-Cells) have been investigated for their utility in providing neuroprotection following transplantation into models of amyotrophic lateral sclerosis (ALS) and have been granted a Food and Drug Administration (FDA) Investigational New Drug (IND) for intraspinal transplantation in ALS patients. Furthermore, clinical development of these cells for therapeutic use will rely on the ability to track the cells using noninvasive imaging methodologies as well as the verification that the transplanted GRPs have disease-relevant activity. As a first step in development, we investigated the use of a perfluorocarbon (PFC) dual-modal ( 19 F magnetic resonance imaging [MRI] and fluorescence) tracer agent to label Q-Cells in culture and following spinal cord transplantation. PFCs have a number of potential benefits that make them appealing for clinical use. They are quantitative, noninvasive, biologically inert, and highly specific. In this study, we developed optimized PFC labeling protocols for Q-Cells and demonstrate that PFCs do not significantly alter the glial identity of Q-Cells. We also show that PFCs do not interfere with the capacity for differentiation into astrocytes either in vitro or following transplantation into the ventral horn of the mouse spinal cord, and can be visualized in vivo by hot spot 19 F MRI. These studies provide a foundation for further preclinical development of PFCs within the context of evaluating Q-Cell transplantation in the brain and spinal cord of future ALS patients using 19 F MRI. Stem Cells Translational Medicine 2019;8:355–365 : Abstract : We investigated the use of a perfluorocarbon dual—modal ( 19 F magnetic resonance imaging and fluorescence) tracer agent to label human glial progenitor (Q-Cells) in culture and following spinal cord transplantation. Immunohistochemistry shows perinuclear localization of internalized perfluorocarbon in a differentiated Q-Cell expressing glial fibrillary acidic protein. These studies provide a foundation for preclinical development of perfluorocarbons for tracking Q-Cells by 19 F magnetic resonance imaging after transplantation (scale bar = 10 μm).