P3‐136: A Genetically Immortalized Human Stem Cell Line: A Promising New Tool for Alzheimer’s Disease Therapy

Abstract

Amyloid-β peptides and hyper-phosphorylated tau are the main pathological hallmarks of Alzheimer's disease (AD). Given the recent failure of several large-scale clinical trials and the lack of disease-modifying pharmacological treatments, there is an urgent need to develop alternative therapies. A clinical grade human CTX0E03 neural stem cell line has recently passed phase I trials in people with stroke. However, this cell line has not been investigated in other neurodegenerative disorders. This study investigates the survival of CTX0E03 cells under conditions based on the underlying AD pathology. Cell viability assays showed a concentration dependence of this cell line to the toxic effects of Aβ 1-42 , but not Aβ 1-40 , and okadaic acid, a phosphatase 2A inhibitor. Notably, CTX0E03 cell line displayed toxicity at concentrations significantly higher than both rat neural stem cells and those previously reported for primary cultures. These results suggest CTX0E03 cells could be developed for clinical trials in AD patients.

Practical Use of Immortalized Cells in Medicine: Current Advances and Future Perspectives

“…The ability of CTX0E03 cells to survive in an in vitro model of Alzheimer’s disease was assessed by Puangmalai et al by culturing in an environment containing various concentrations of amyloid β or okadaic acid, a protein phosphatase inhibitor that creates a high concentration of phosphorylated tau protein. The CTX0E03 cell line demonstrated similar or better survival rates compared to primary cultured rat neuronal stem cells, making them potential candidates for cell therapy in Alzheimer’s disease [ 42 ]. At the same time, the study of Yoon et al demonstrated the effectiveness of using CTX0E03 cells for the treatment of Huntington’s disease in the quinolinic acid-lesioned mouse model [ 43 ].…”

“…Despite some issues with the methodology of clinical trials (small sample size, wide range of time elapsed since stroke, lack of female patients in phase I [ 44 , 45 ]), many preclinical [ 42 , 43 , 46 ] and clinical studies demonstrate that the CTX0E03 cell line is a promising therapeutic tool with a significant neuroregenerative potential, both in models of ischemic damage and in models of neurodegenerative diseases. The advantages of this line in comparison with the primary culture are obvious, such as the absence of the need for obtaining and isolating material and the standardization of research results.…”