Patient-Specific and Regional Factors Influencing Proliferation Dynamics of Adult Human Neural Stem/Progenitor Cells from Spinal Cord Tissue

Abstract

Direct comparison of proliferation characteristics between primary adult human neural stem/progenitor cells (NSPCs) and their animal counterparts has been challenging due to the difficulty in obtaining viable adult human spinal cord tissue. Here, we present the first assessment of proliferation rates of NSPCs derived from adult human spinal cord samples and the development of a multivariate linear regression model to predict their proliferation dynamics. We cultured NSPCs from 42 spinal cord tissue samples, sourced from 27 adult human organ donors, to examine their doubling times and proliferation rates. Key characteristics, including sex, age, spinal cord region (thoracic, lumbar, conus), neurological conditions (e.g., epilepsy, Parkinson's disease, schizophrenia), and substance use (alcohol misuse, intravenous drug use, polydrug use) were analyzed for their correlation with NSPC proliferative behavior. Immunocytochemical analysis confirmed the multipotency of these NSPCs, indicating their capability to differentiate into multiple neural lineages. A multivariate linear regression model was developed to predict NSPC proliferation rates, encoding categorical variables as integers and using binary values for neurological conditions and substance use, with 7-fold cross-validation ensuring model robustness. The model demonstrated high predictive performance (MSE = 0.006335, MAE = 0.0217, R² = 0.887), and validation on an independent cohort yielded an R² of 0.916 and an MSE of 0.018003. Our findings revealed a significant decline in NSPC proliferation in older individuals and those with substance use histories, while NSPCs from the conus region exhibited higher proliferation rates. Furthermore, neurological conditions, such as epilepsy and Parkinson's disease, were found to correlate with reduced NSPC proliferation rates, highlighting the impact of underlying pathology on stem cell dynamics.