Poster - #UCLA-37 - Keywords: traumatic brain injury, neural stem cells, LM-NSC008 allogeneic cells, L-Myc immortalized stem cells

Biodistribution of L-myc Immortalized Human Stem Cells from Olfactory Bulb to TBI sites in a Rat Model of Controlled Cortical Impact Injury

Mari Amirbekyan1, Eleni H. Moschonas2, Jeffrey P. Cheng2, Vikram Adhikarla3, Russell C. Rockne3, Corina O. Bondi2, Anthony E. Kline2 and Margarita Gutova1* 
1Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 2Physical Medicine & Rehabilitation, Critical Care Medicine, Psychology, Center for Neuroscience, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 3Division of Mathematical Oncology, Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA

ABSTRACT:
Traumatic brain injury (TBI) often results in long-term neurological disabilities and affects ten million individuals worldwide each year (Hyder et al., 2007).  In the United States, the incidence is 2.8 million per year (Taylor et al., 2017). Although various approaches have shown benefits in the laboratory, successful clinical translation has been essentially nonexistent. This dismal situation has motivated development of other alternative therapeutic strategies. Neural stem cells (NSCs) are attractive candidates for restoration of brain function after TBI as they inherently migrate to damaged sites, where they contribute neurotrophic factors to suppress inflammation, protect against further neuronal loss, promote recovery of existing damaged neurons, and possibly replace lost neurons and other cells (Gutova et al., 2013). However, a major challenge to successful NSC-based therapy is ensuring that sufficient numbers of cells reach damaged and non-functioning regions. We and others have explored intravenous (IV) delivery of NSCs to the CNS, as well as intracranial (IC) injection and intranasal (IN) inhalation (Balyasnikova et al., 2014; Gutova et al., 2013). Although IV injected NSCs localize to damaged tissue, they show limited accumulation in the brain (less than 1% of injected NSCs) (Loebinger et al., 2009; Barish et al., 2017). Additionally, IV administration of NSCs can trigger adverse immune responses and other systemic complications. Though IC administration of NSCs avoids these potential systemic reactions (Barish et al., 2017), it is invasive, inefficient, costly, potentially damaging to normal brain tissue, and places patients at greater risk. The inherent limitations of IV and IC administration highlight the merit in evaluating IN delivery, which is less invasive and can be performed over a course of repeated NSC administrations (Balyasnikova et al., 2014). We hypothesized that intranasally-administered L-MYC-immortalized human NSCs (LM-NSC008 cells) accumulate in damaged brain tissue and facilitate recovery after TBI.