Introduction: Clinical trials using stem cells to treat Amyotrophic Lateral Sclerosis (ALS) have been promising. However, most of these trials lack an appropriate approach for tracking the cells. The goal of the present study is to develop and validate a rapidly translatable methodology for in vivo visualization and post-mortem identification of stem cells transplanted into the spinal cord of ALS patients.
Methods: GDNF-secreting human neural stem cells were labeled with Ferraheme (AMAG Pharmaceuticals, Inc, Lexington, MA, USA), an FDA-approved ultra-small superparamagnetic iron oxide nanoparticle (USPIO). Ferraheme nanoparticles were used as an intracellular MRI contrast agent because they produce local field inhomogeneities that decrease the T2 signal on Magnetic Resonance Imaging (MRI). Labeled cells were assessed for functionality and labeling success in vitro. Labeled cells were directly injected in to the spinal cord of healthy rats, ALS SOD-1 rats, and healthy pigs to assess in vivo visualization and cell function. Multiple 2µL and 10µL cell injections with a concentration of 10,000 cells/µL were done in rodents and pigs, respectively. Rodents were imaged on a 9.4T MRI animal scanner and pigs on a 3T full body MRI scanner.
Results: In vitro cell viability, proliferation, and differentiation were not altered by the labeling protocol. The in vitro detection limit of USPIO labeled cells was 20,000 cells using a 3T full body MRI scanner. Transplanted labeled cell grafts were visualized in vivo with MRI in the spinal cord of both rodents and pigs. Cells were visualized at least two weeks after transplantation in the rodents.
Conclusions: USPIO particles serve as a valuable tool for tracking neural stem cells in vivo in the spinal cord. Additional work must be completed to assess the effect these particles have on cell function.
Patient Care: Developing a method for in vivo tracking and post-mortem identification of neural stem cells will help to optimize future clinical trials using stem cells in the spinal cord. It will allow the investigators to have a much better understanding of the fate of the cells.
Learning Objectives: By the conclusion of this session, participants should be able to describe the importance of tracking stem cell grafts in vivo.