The genetically modified polysialylated form of neural cell adhesion molecule-positive cells for potential treatment of X-linked adrenoleukodystrophy

Purpose: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. Materials and Methods: PSA-NCAM⁺ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM⁺ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. Results: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM⁺ cells, and can enhance PSA-NCAM⁺ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. Conclusion: These results may provide new insights into investigation of PSA-NCAM⁺ cells for therapeutic application to X-linked adrenoleukodystrophy.