Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease

• DOI: 10.5966/sctm.2015-0103
• Publication Date: 2016-01-08T03:53:45Z
• Authors: Lisa M. McGinley; Erika Sims; J. Simon Lunn; Osama N. Kashlan; Kevin S. Chen; Elizabeth S. Bruno; Crystal M. Pacut; Tom Hazel; Karl Johe; Stacey A. Sakowski; Eva L. Feldman
• Keywords: Neuregulin; Synaptogenesis

Abstract Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying pathologies very little progress has been made develop effective drug treatments. Cellular therapies impact by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate into cord, form synapses host, improve inflammation, reduce disease-associated pathologies. Our current goal similar “best in class” cellular therapy for AD. Here, characterize novel human cortex-derived NSC line modified express insulin-like growth factor-I (IGF-I), HK532-IGF-I. Because IGF-I promotes neurogenesis synaptogenesis vivo, this enhanced offers additional environmental enrichment, neuroprotection, multifaceted approach treating complex AD We show autocrine production does not cell secretome or normal functions, including proliferation, migration, maintenance progenitor status. However, HK532-IGF-I preferentially differentiate gamma-aminobutyric acid-ergic neurons, subtype dysregulated AD; produce vascular endothelial factor levels; display an neuroprotective capacity vitro. also demonstrate survive peri-hippocampal transplantation murine model exhibit long-term persistence targeted brain areas. conclusion, believe harnessing benefits together will provide optimal therapeutic benefit patients, our findings support further preclinical development disease-modifying intervention Significance There no cure means prevention. treatments temporarily slow dementia symptoms but ultimately fail alter course. Given prevalence increasingly aging population, alternative strategies are necessary. traditional, discovery This study describes produces amounts factors beneficial environment. Findings potentially safe clinically translatable patients