EXTH-49. IN VIVO ANALYSES OF LONG-TERM STABILITY AND DISTRIBUTION PATTERNS OF L-MYC IMMORTALIZED HUMAN NEURAL STEM CELLS

Preclinical studies indicate that neural stem cells (NSCs) can limit or reverse central nervous system (CNS) damage through delivery of therapeutic agents of cell regeneration. Clinical translation of cell-based therapies raises concerns about the long-term stability, absence of tumorigenicity, and manufacturing time required to produce therapeutic cells in quantities sufficient for clinical use. Allogeneic NSC lines are in growing demand due to challenges inherent in employing autologous stem cells, including production costs limiting availability to patients. Here, we demonstrate the long-term stability of L-MYC immortalized human NSCs (LM-NSC008) in vivo, including engraftment, migration, and absence of tumorigenicity of LM-NSC008 cells resident in mouse brains for over nine months. These are all properties favoring potential use of these allogeneic NSCs in clinical settings. We also examined the distributions of engrafted LM-NSC008 cells, and developed computational techniques to analyze NSC migration characteristics in relation to intrinsic brain structure (as assessed by light microscopy). This computational analysis of NSC distributions following implantation provides proof-of-concept for the development of computational models that can be used clinically to predict NSC migration paths in patients. Previously, models of preferential malignant tumor cell migration along white matter tracts have been used to predict their final distributions. We suggest that quantitative measures of tissue orientation and white matter tracts determined from MR images can be used in a diffusion tensor imaging tractography-like approach to describe the most likely migration routes and final distributions of NSCs administered in a clinical setting. Such a model could be very useful in choosing the optimal locations for NSC administration to patients to achieve maximum therapeutic effects.