Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19F Magnetic Resonance Imaging

Jean-Philippe Richard, Uzma Hussain, Sarah Gross, Arens Taga, Mehreen Kouser, Akshata Almad, James T. Campanelli, Jeff W Bulte, Nicholas J Maragakis

Research output: Contribution to journalArticle

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 (19F 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 19F 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 19F MRI. Stem Cells Translational Medicine 2019.

Original languageEnglish (US)
JournalStem cells translational medicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Fluorocarbons
Neuroglia
Magnetic Resonance Imaging
Amyotrophic Lateral Sclerosis
Transplantation
Spinal Cord
Stem Cells
Investigational Drugs
Translational Medical Research
Cell Transplantation
Stem Cell Transplantation
Therapeutic Uses
United States Food and Drug Administration
Fluorescent Dyes
Astrocytes
Cell Movement
Cell Survival
Central Nervous System
Cell Culture Techniques
Brain

Keywords

  • F
  • Cell tracking
  • Fluorine-19
  • MRI
  • Perfluorocarbon
  • Stem cell
  • Transplantation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19F Magnetic Resonance Imaging. / Richard, Jean-Philippe; Hussain, Uzma; Gross, Sarah; Taga, Arens; Kouser, Mehreen; Almad, Akshata; Campanelli, James T.; Bulte, Jeff W; Maragakis, Nicholas J.

In: Stem cells translational medicine, 01.01.2019.

Research output: Contribution to journalArticle

Richard, Jean-Philippe ; Hussain, Uzma ; Gross, Sarah ; Taga, Arens ; Kouser, Mehreen ; Almad, Akshata ; Campanelli, James T. ; Bulte, Jeff W ; Maragakis, Nicholas J. / Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for 19F Magnetic Resonance Imaging. In: Stem cells translational medicine. 2019.
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